Skip to main content

Advertisement

SpringerLink
Log in

Does PGC1α/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders?

  • Original Paper
  • Published:
NeuroMolecular Medicine Aims and scope Submit manuscript

Abstract

Neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases have high prevalence among the elderly. Many strategies have been established to alleviate the symptoms experienced by affected individuals. Recent studies have shown that exercise helps patients with neurological disorders to regain lost physical abilities. PGC1α/FNDC5/BDNF has emerged recently as a critical pathway for neuroprotection. PGC1α is a highly conserved co-activator of transcription factors that preserves and protects neurons against destruction. PGC1α regulates FNDC5 and its processed and secreted peptide Irisin, which has been proposed to play a critical role in energy expenditure and to promote neural differentiation of mouse embryonic stem cells. FNDC5 may also increase the expression of the neurotrophic factor BDNF, a neuroprotective agent, in the hippocampus. BDNF is secreted from hippocampus, amygdala, cerebral cortex and hypothalamus neurons and initiates intracellular signaling pathways through TrkB receptors. These pathways have positive feedback on CREB activities and lead to enhancement in PGC1α expression in neurons. Therefore, FNDC5 could behave as a key regulator in neuronal survival and development. This review presents recent findings on the PGC1α/FNDC5/BDNF pathway and its role in neuroprotection, and discusses the controversial promise of irisin as a mediator of the positive benefits of exercise.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

6-OHDA:

6-Hydroxy dopamine

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

ATP:

Adenosine triphosphate

BDNF:

Brain-derived neurotrophic factor

CNS:

Central nervous system

CREB:

cAMP-responsive element binding protein

DHA:

Docosahexaenoicacid

ERRα:

Estrogen-related receptor alpha

ETC:

Electron transport chain

FA:

Friedreich’s ataxia

FNDC5:

Fibronectin type III domain-containing 5

GPx:

Glutathione peroxidase

HD:

Huntington’s disease

KSS:

Kearns–Sayre syndrome

LTP:

Long-term potentiation

MAO:

Monoamine oxidase

MAPK:

Mitogen-activated protein kinase

MELSAS:

Mitochondrial encephalopathy lactic acidosis and strokes

mHtt:

Mutant huntingtin protein

Mn-SOD:

Manganese superoxide dismutase

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NMDA:

N-Methyl-d-aspartate

NRF:

Nuclear respiratory factor

OXPHOS:

Oxidative phosphorylation system

PARIS:

Parkin-interacting substrate

PBDs:

Peroxisome biogenesis disorders

PD:

Parkinson’s disease

PEDs:

Peroxisomal enzyme deficiencies

PEP:

Peroxisomal protein

PGC1α:

Peroxisome proliferator-activated receptor γ co-activator α

PI3K:

Phosphatidyl inositol-3-kinase

PLCγ:

Phospholipase C-γ

PPARα:

Peroxisome proliferator receptor alpha

PUFAs:

Polyunsaturated fatty acids

ROS:

Reactive oxygen species

SIRT1:

Sirtunin1

SNP:

Single-nucleotide polymorphism

SOD:

Superoxide dismutase

TAF4:

Transcription initiation factor 4

TFAM:

Mitochondrial transcription factor A

TR:

Thyroid receptor

TrkB:

Tyrosine kinase receptor B

VDAC:

Voltage-dependent anion channels

References

  • Ahlskog, J. E. (2011). Cheaper, simpler, and better: Tips for treating seniors with Parkinson disease. Mayo Clinic Proceedings, 86, 1211–1216.

    Article  PubMed Central  PubMed  Google Scholar 

  • Albrecht, E., Norheim, F., Thiede, B., Holen, T., Ohashi, T., Schering, L., et al. (2015). Irisin—A myth rather than an exercise-inducible myokine. Scientific reports, 5, 8889.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Amadoro, G., Corsetti, V., Florenzano, F., Atlante, A., Bobba, A., Nicolin, V., et al. (2014). Morphological and bioenergetic demands underlying the mitophagy in post-mitotic neurons: the pink-parkin pathway. Front Aging Neurosci, 6, 18.

    Article  PubMed Central  PubMed  Google Scholar 

  • Andreyev, A. Y., Kushnareva, Y. E., Murphy, A. N., & Starkov, A. A. (2015). Mitochondrial ROS metabolism: 10 years later. Biochemistry (Mosc), 80, 517–531.

    Article  CAS  Google Scholar 

  • Antonenkov, V. D., Grunau, S., Ohlmeier, S., & Hiltunen, J. K. (2010). Peroxisomes are oxidative organelles. Antioxidants and Redox Signaling, 13, 525–537.

    Article  PubMed  CAS  Google Scholar 

  • Ayala, A., Muñoz, M. F., & Argüelles, S. (2014). Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity, 2014, 360438.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Aydin, S., Kuloglu, T., Eren, M. N., Celik, A., Yilmaz, M., Kalayci, M., et al. (2014). Cardiac, skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: Cardiac muscle produces more irisin than skeletal muscle. Peptides, 52, 68–73.

    Article  PubMed  CAS  Google Scholar 

  • Baes, M., & Aubourg, P. (2009). Peroxisomes, myelination, and axonal integrity in the CNS. Neuroscientist, 15, 367–379.

    Article  PubMed  CAS  Google Scholar 

  • Baes, M., & Van Veldhoven, P. P. (2006). Generalised and conditional inactivation of Pex genes in mice. Biochimica et Biophysica Acta, 1763, 1785–1793.

    Article  PubMed  CAS  Google Scholar 

  • Baines, C. P. (2010). Role of the mitochondrion in programmed necrosis. Frontiers in Physiology, 1, 156.

    Article  PubMed Central  PubMed  Google Scholar 

  • Balaban, R. S., Nemoto, S., & Finkel, T. (2005). Mitochondria, oxidants, and aging. Cell, 120, 483–495.

    Article  PubMed  CAS  Google Scholar 

  • Bennett, S. A., Valenzuela, N., Xu, H., Franko, B., Fai, S., & Figeys, D. (2013). Using neurolipidomics to identify phospholipid mediators of synaptic (dys)function in Alzheimer’s Disease. Frontiers in Physiology, 4, 168.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Binder, D. K., & Scharfman, H. E. (2004). Brain-derived neurotrophic factor. Growth Factors, 22, 123–131.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Blesa, J., Trigo-Damas, I., Quiroga-Varela, A., Jackson-Lewis, V.R. (2015). Oxidative stress and Parkinson’s disease. Front Neuroanat, 9, 91.

    PubMed Central  PubMed  Google Scholar 

  • Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., et al. (2012). A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 481, 463–468.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Bordt, E.A.,& Polster, B.M. (2014). NADPH oxidase- and mitochondria-derived reactive oxygen species in proinflammatory microglial activation: a bipartisan affair? Free Radic Biol Med, 76, 34–46.

    Article  PubMed  CAS  Google Scholar 

  • Braverman, N. E., & Moser, A. B. (2012). Functions of plasmalogen lipids in health and disease. Biochimica et Biophysica Acta, 1822, 1442–1452.

    Article  PubMed  CAS  Google Scholar 

  • Calon, F., Lim, G. P., Yang, F., Morihara, T., Teter, B., Ubeda, O., et al. (2004). Docosahexaenoic acid protects from dendritic pathology in an Alzheimer’s disease mouse model. Neuron, 43, 633–645.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Carlezon, W. A., Duman, R. S., & Nestler, E. J. (2005). The many faces of CREB. Trends in Neurosciences, 28, 436–445.

    Article  PubMed  CAS  Google Scholar 

  • Castillo-Quan, J. I. (2011). Parkin’ control: Regulation of PGC-1α through PARIS in Parkinson’s disease. Disease Models and Mechanisms, 4, 427–429.

    Article  PubMed Central  PubMed  Google Scholar 

  • Chapman, P. F., White, G. L., Jones, M. W., Cooper-Blacketer, D., Marshall, V. J., Irizarry, M., et al. (1999). Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nature Neuroscience, 2, 271–276.

    Article  PubMed  CAS  Google Scholar 

  • Chaturvedi, R. K., & Beal, M. F. (2013). Mitochondrial diseases of the brain. Free Radical Biology and Medicine, 63, 1–29.

    Article  PubMed  CAS  Google Scholar 

  • Chen, H., McCaffery, J. M., & Chan, D. C. (2007). Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell, 130, 548–562.

    Article  PubMed  CAS  Google Scholar 

  • Chen, Z. Y., Patel, P. D., Sant, G., Meng, C. X., Teng, K. K., Hempstead, B. L., & Lee, F. S. (2004). Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. Journal of Neuroscience, 24, 4401–4411.

    Article  PubMed  CAS  Google Scholar 

  • Ciccone, S., Maiani, E., Bellusci, G., Diederich, M., & Gonfloni, S. (2013). Parkinson’s disease: A complex interplay of mitochondrial DNA alterations and oxidative stress. International Journal of Molecular Sciences, 14, 2388–2409.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Clark, J., Reddy, S., Zheng, K., Betensky, R. A., & Simon, D. K. (2011). Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson’s disease. BMC Medical Genetics, 12, 69.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Connolly, A. M., Chez, M., Streif, E. M., Keeling, R. M., Golumbek, P. T., Kwon, J. M., et al. (2006). Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau–Kleffner syndrome, and epilepsy. Biological Psychiatry, 59, 354–363.

    Article  PubMed  CAS  Google Scholar 

  • Conquer, J. A., Tierney, M. C., Zecevic, J., Bettger, W. J., & Fisher, R. H. (2000). Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia, and cognitive impairment. Lipids, 35, 1305–1312.

    Article  PubMed  CAS  Google Scholar 

  • Corona, J. C., & Duchen, M. R. (2015). PPARγ and PGC-1α as therapeutic targets in Parkinson’s. Neurochemical Research, 40, 308–316.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Cotman, C. W., Berchtold, N. C., & Christie, L. A. (2007). Exercise builds brain health: Key roles of growth factor cascades and inflammation. Trends in Neurosciences, 30, 464–472.

    Article  PubMed  CAS  Google Scholar 

  • Cui, L., Jeong, H., Borovecki, F., Parkhurst, C. N., Tanese, N., & Krainc, D. (2006). Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell, 127, 59–69.

    Article  PubMed  CAS  Google Scholar 

  • del Río, L. A., Corpas, F. J., Sandalio, L. M., Palma, J. M., Gómez, M., & Barroso, J. B. (2002). Reactive oxygen species, antioxidant systems and nitric oxide in peroxisomes. Journal of Experimental Botany, 53, 1255–1272.

    Article  PubMed  Google Scholar 

  • Desai, N. S., Rutherford, L. C., & Turrigiano, G. G. (1999). BDNF regulates the intrinsic excitability of cortical neurons. Learning and Memory, 6, 284–291.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Dun, S. L., Lyu, R. M., Chen, Y. H., Chang, J. K., Luo, J. J., & Dun, N. J. (2013). Irisin-immunoreactivity in neural and non-neural cells of the rodent. Neuroscience, 240, 155–162.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Dwivedi, Y. (2009). Brain-derived neurotrophic factor: Role in depression and suicide. Neuropsychiatric Disease and Treatment, 5, 433–449.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Edmondson, D. E. (2014). Hydrogen peroxide produced by mitochondrial monoamine oxidase catalysis: biological implications. Current Pharmaceutical Design, 20, 155–160.

    Article  PubMed  CAS  Google Scholar 

  • Eichner, L. J., & Giguère, V. (2011). Estrogen related receptors (ERRs): A new dawn in transcriptional control of mitochondrial gene networks. Mitochondrion, 11, 544–552.

    Article  PubMed  CAS  Google Scholar 

  • Erickson, H. P. (2013). Irisin and FNDC5 in retrospect: An exercise hormone or a transmembrane receptor? Adipocyte, 2, 289–293.

    Article  PubMed Central  PubMed  Google Scholar 

  • Evans, R. M. (2005). The nuclear receptor superfamily: A rosetta stone for physiology. Molecular Endocrinology, 19, 1429–1438.

    Article  PubMed  CAS  Google Scholar 

  • Exner, N., Lutz, A.K., Haass, C., Winklhofer, K.F. (2012). Mitochondrial dysfunction in Parkinson’s disease: molecular mechanisms and pathophysiological consequences. EMBO J, 31(14), 3038–3062.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Farrar, G. J., Chadderton, N., Kenna, P. F., & Millington-Ward, S. (2013). Mitochondrial disorders: Aetiologies, models systems, and candidate therapies. Trends in Genetics, 29, 488–497.

    Article  PubMed  CAS  Google Scholar 

  • Ferreiro, E., Baldeiras, I., Ferreira, I. L., Costa, R. O., Rego, A. C., Pereira, C. F., & Oliveira, C. R. (2012). Mitochondrial- and endoplasmic reticulum-associated oxidative stress in Alzheimer’s disease: From pathogenesis to biomarkers. International Journal of Cell Biology, 2012, 735206.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ferrer-Martínez, A., Ruiz-Lozano, P., & Chien, K. R. (2002). Mouse PeP: A novel peroxisomal protein linked to myoblast differentiation and development. Developmental Dynamics, 224, 154–167.

    Article  PubMed  CAS  Google Scholar 

  • Fiore, M., Chaldakov, G. N., & Aloe, L. (2009). Nerve growth factor as a signaling molecule for nerve cells and also for the neuroendocrine-immune systems. Reviews in the Neurosciences, 20, 133–145.

    Article  PubMed  CAS  Google Scholar 

  • Forouzanfar, M., Rabiee, F., Ghaedi, K., Beheshti, S., Tanhaei, S., Shoaraye Nejati, A., et al. (2015). Fndc5 overexpression facilitated neural differentiation of mouse embryonic stem cells. Cell Biology International, 39, 629–637.

    Article  PubMed  CAS  Google Scholar 

  • Fransen, M., Nordgren, M., Wang, B., & Apanasets, O. (2012). Role of peroxisomes in ROS/RNS-metabolism: Implications for human disease. Biochimica et Biophysica Acta, 1822, 1363–1373.

    Article  PubMed  CAS  Google Scholar 

  • Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M. S., et al. (2002). alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nature Cell Biology, 4, 160–164.

    Article  PubMed  CAS  Google Scholar 

  • Ghahrizjani, F. A., Ghaedi, K., Salamian, A., Tanhaei, S., Nejati, A. S., Salehi, H., et al. (2015). Enhanced expression of FNDC5 in human embryonic stem cell-derived neural cells along with relevant embryonic neural tissues. Gene, 557, 123–129.

    Article  PubMed  CAS  Google Scholar 

  • Giampà, C., Montagna, E., Dato, C., Melone, M. A., Bernardi, G., & Fusco, F. R. (2013). Systemic delivery of recombinant brain derived neurotrophic factor (BDNF) in the R6/2 mouse model of Huntington’s disease. PLoS One, 8, e64037.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ginsberg, L., Rafique, S., Xuereb, J. H., Rapoport, S. I., & Gershfeld, N. L. (1995). Disease and anatomic specificity of ethanolamine plasmalogen deficiency in Alzheimer’s disease brain. Brain Research, 698, 223–226.

    Article  PubMed  CAS  Google Scholar 

  • Goncalves, R. L., Rothschild, D. E., Quinlan, C. L., Scott, G. K., Benz, C. C., & Brand, M. D. (2014). Sources of superoxide/H2O2 during mitochondrial proline oxidation. Redox Biology, 2, 901–909.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Green, D. R., & Kroemer, G. (2004). The pathophysiology of mitochondrial cell death. Science, 305, 626–629.

    Article  PubMed  CAS  Google Scholar 

  • Greenberg, M. E., Xu, B., Lu, B., & Hempstead, B. L. (2009). New insights in the biology of BDNF synthesis and release: implications in CNS function. Journal of Neuroscience, 29, 12764–12767.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Guo, C., Sun, L., Chen, X., & Zhang, D. (2013). Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regeneration Research, 8, 2003–2014.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Haas, R. H., Parikh, S., Falk, M. J., Saneto, R. P., Wolf, N. I., Darin, N., et al. (2008). The in-depth evaluation of suspected mitochondrial disease. Molecular Genetics and Metabolism, 94, 16–37.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Han, J.Y., Kim, J.S., Son, J.H. (2014). Mitochondrial homeostasis molecules: regulation by a trio of recessive Parkinson's disease genes. Exp Neurobiol, 23(4), 345–351.

    Article  PubMed Central  PubMed  Google Scholar 

  • Handschin, C. (2009). The biology of PGC-1α and its therapeutic potential. Trends in Pharmacological Sciences, 30, 322–329.

    Article  PubMed  CAS  Google Scholar 

  • Hashemi, M. S., Ghaedi, K., Salamian, A., Karbalaie, K., Emadi-Baygi, M., Tanhaei, S., et al. (2013). Fndc5 knockdown significantly decreased neural differentiation rate of mouse embryonic stem cells. Neuroscience, 231, 296–304.

    Article  PubMed  CAS  Google Scholar 

  • Herben-Dekker, M., van Oostrom, J. C., Roos, R. A., Jurgens, C. K., Witjes-Ané, M. N., Kremer, H. P., et al. (2014). Striatal metabolism and psychomotor speed as predictors of motor onset in Huntington’s disease. Journal of Neurology, 261, 1387–1397.

    Article  PubMed  CAS  Google Scholar 

  • Huang, E. J., & Reichardt, L. F. (2001). Neurotrophins: Roles in neuronal development and function. Annual Review of Neuroscience, 24, 677–736.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hwang, O. (2013). Role of oxidative stress in Parkinson’s disease. Exp Neurobiol, 22(1), 11–17.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ivanov, I.P., Firth, A.E., Michel, A.M., Atkins, J.F., Baranov, P.V. (2011). Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences. Nucleic Acids Res, 39(10), 4220–4234.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ivashchenko, O., Van Veldhoven, P. P., Brees, C., Ho, Y. S., Terlecky, S. R., & Fransen, M. (2011). Intraperoxisomal redox balance in mammalian cells: Oxidative stress and interorganellar cross-talk. Molecular Biology of the Cell, 22, 1440–1451.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Jin, Y. N., & Johnson, G. V. (2010). The interrelationship between mitochondrial dysfunction and transcriptional dysregulation in Huntington disease. Journal of Bioenergetics and Biomembranes, 42, 199–205.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Johnson, W. T., Johnson, L. A., & Lukaski, H. C. (2005). Serum superoxide dismutase 3 (extracellular superoxide dismutase) activity is a sensitive indicator of Cu status in rats. Journal of Nutritional Biochemistry, 16, 682–692.

    Article  PubMed  CAS  Google Scholar 

  • Johri, A., & Beal, M. F. (2012). Mitochondrial dysfunction in neurodegenerative diseases. Journal of Pharmacology and Experimental Therapeutics, 342, 619–630.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kalmijn, S., Launer, L. J., Ott, A., Witteman, J. C., Hofman, A., & Breteler, M. M. (1997). Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Annals of Neurology, 42, 776–782.

    Article  PubMed  CAS  Google Scholar 

  • Kassmann, C. M., Lappe-Siefke, C., Baes, M., Brügger, B., Mildner, A., Werner, H. B., et al. (2007). Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes. Nature Genetics, 39, 969–976.

    Article  PubMed  CAS  Google Scholar 

  • Katsouri, L., Parr, C., Bogdanovic, N., Willem, M., & Sastre, M. (2011). PPARγ co-activator-1α (PGC-1α) reduces amyloid-β generation through a PPARγ-dependent mechanism. Journal of Alzheimer’s Disease, 25, 151–162.

    PubMed  CAS  Google Scholar 

  • Kelly, D. P., & Scarpulla, R. C. (2004). Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes and Development, 18, 357–368.

    Article  PubMed  CAS  Google Scholar 

  • Keogh, M.J., Chinnery, P.F. (2015). Mitochondrial DNA mutations in neurodegeneration. Biochim Biophys Acta, 1847(11), 1401–1411.

    Article  CAS  Google Scholar 

  • Kobilo, T., Liu, Q. R., Gandhi, K., Mughal, M., Shaham, Y., & van Praag, H. (2011). Running is the neurogenic and neurotrophic stimulus in environmental enrichment. Learning and Memory, 18, 605–609.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Koepke, J. I., Nakrieko, K. A., Wood, C. S., Boucher, K. K., Terlecky, L. J., Walton, P. A., & Terlecky, S. R. (2007). Restoration of peroxisomal catalase import in a model of human cellular aging. Traffic, 8, 1590–1600.

    Article  PubMed  CAS  Google Scholar 

  • Kotiadis, V. N., Duchen, M. R., & Osellame, L. D. (2014). Mitochondrial quality control and communications with the nucleus are important in maintaining mitochondrial function and cell health. Biochimica et Biophysica Acta, 1840, 1254–1265.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kou, J., Kovacs, G. G., Höftberger, R., Kulik, W., Brodde, A., Forss-Petter, S., et al. (2011). Peroxisomal alterations in Alzheimer’s disease. Acta Neuropathologica, 122, 271–283.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kressler, D., Schreiber, S. N., Knutti, D., & Kralli, A. (2002). The PGC-1-related protein PERC is a selective coactivator of estrogen receptor alpha. Journal of Biological Chemistry, 277, 13918–13925.

    Article  PubMed  CAS  Google Scholar 

  • Lee, P., Linderman, J. D., Smith, S., Brychta, R. J., Wang, J., Idelson, C., et al. (2014). Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metabolism, 19, 302–309.

    Article  PubMed  CAS  Google Scholar 

  • Legros, F., Malka, F., Frachon, P., Lombès, A., & Rojo, M. (2004). Organization and dynamics of human mitochondrial DNA. Journal of Cell Science, 117, 2653–2662.

    Article  PubMed  CAS  Google Scholar 

  • Lezi, E., & Swerdlow, R. H. (2012). Mitochondria in neurodegeneration. Advances in Experimental Medicine and Biology, 942, 269–286.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lin, M. T., & Beal, M. F. (2006). Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 443, 787–795.

    Article  PubMed  CAS  Google Scholar 

  • Lin, J., Puigserver, P., Donovan, J., Tarr, P., & Spiegelman, B. M. (2002a). Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta), a novel PGC-1-related transcription coactivator associated with host cell factor. Journal of Biological Chemistry, 277, 1645–1648.

    Article  PubMed  CAS  Google Scholar 

  • Lin, M.Y., & Sheng, Z.H. (2015). Regulation of mitochondrial transport in neurons. Exp Cell Res, 334(1), 35–44.

    Article  PubMed  CAS  Google Scholar 

  • Lin, J., Wu, P. H., Tarr, P. T., Lindenberg, K. S., St-Pierre, J., Zhang, C. Y., et al. (2004). Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell, 119, 121–135.

    Article  PubMed  CAS  Google Scholar 

  • Lin, J., Wu, H., Tarr, P. T., Zhang, C. Y., Wu, Z., Boss, O., et al. (2002b). Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature, 418, 797–801.

    Article  PubMed  CAS  Google Scholar 

  • Lodhi, I. J., & Semenkovich, C. F. (2014). Peroxisomes: A nexus for lipid metabolism and cellular signaling. Cell Metabolism, 19, 380–392.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lopez-Huertas, E., Charlton, W. L., Johnson, B., Graham, I. A., & Baker, A. (2000). Stress induces peroxisome biogenesis genes. EMBO Journal, 19, 6770–6777.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mailloux, R. J. (2015). Teaching the fundamentals of electron transfer reactions in mitochondria and the production and detection of reactive oxygen species. Redox Biology, 4, 381–398.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Martin, E., Betuing, S., Pagès, C., Cambon, K., Auregan, G., Deglon, N., et al. (2011). Mitogen- and stress-activated protein kinase 1-induced neuroprotection in Huntington’s disease: role on chromatin remodeling at the PGC-1-alpha promoter. Human Molecular Genetics, 20, 2422–2434.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mattson, M. P. (2012). Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metabolism, 16, 706–722.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • McAllister, A. K. (2001). Neurotrophins and neuronal differentiation in the central nervous system. Cellular and Molecular Life Sciences, 58, 1054–1060.

    Article  PubMed  CAS  Google Scholar 

  • McGill, J. K., & Beal, M. F. (2006). PGC-1alpha, a new therapeutic target in Huntington’s disease? Cell, 127, 465–468.

    Article  PubMed  CAS  Google Scholar 

  • Milnerwood, A. J., & Raymond, L. A. (2010). Early synaptic pathophysiology in neurodegeneration: Insights from Huntington’s disease. Trends in Neurosciences, 33, 513–523.

    Article  PubMed  CAS  Google Scholar 

  • Mochel, F., & Haller, R. G. (2011). Energy deficit in Huntington disease: Why it matters. Journal of Clinical Investigation, 121, 493–499.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Momose, Y., Murata, M., Kobayashi, K., Tachikawa, M., Nakabayashi, Y., Kanazawa, I., & Toda, T. (2002). Association studies of multiple candidate genes for Parkinson’s disease using single nucleotide polymorphisms. Annals of Neurology, 51, 133–136.

    Article  PubMed  CAS  Google Scholar 

  • Monteiro-Junior, R. S., Cevada, T., Oliveira, B. R., Lattari, E., Portugal, E. M., Carvalho, A., & Deslandes, A. C. (2015). We need to move more: Neurobiological hypotheses of physical exercise as a treatment for Parkinson’s disease. Medical Hypotheses,. doi:10.1016/j.mehy.2015.07.011

    PubMed  Google Scholar 

  • Moon, H. S., Dincer, F., & Mantzoros, C. S. (2013). Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis in mouse H19-7 hippocampal cell lines. Metabolism, 62, 1131–1136.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Moreira, P. I., Santos, M. S., Seiça, R., & Oliveira, C. R. (2007). Brain mitochondrial dysfunction as a link between Alzheimer’s disease and diabetes. Journal of the Neurological Sciences, 257, 206–214.

    Article  PubMed  CAS  Google Scholar 

  • Mudò, G., Mäkelä, J., Di Liberto, V., Tselykh, T. V., Olivieri, M., Piepponen, P., et al. (2012). Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease. Cellular and Molecular Life Sciences, 69, 1153–1165.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, M. P. (2009). How mitochondria produce reactive oxygen species. Biochemical Journal, 417, 1–13.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nagley, P., Higgins, G. C., Atkin, J. D., & Beart, P. M. (2010). Multifaceted deaths orchestrated by mitochondria in neurones. Biochimica et Biophysica Acta, 1802, 167–185.

    Article  PubMed  CAS  Google Scholar 

  • Nicholls, D. G. (2008). Oxidative stress and energy crises in neuronal dysfunction. Annals of the New York Academy of Sciences, 1147, 53–60.

    Article  PubMed  CAS  Google Scholar 

  • Nixon, R. A., Cataldo, A. M., & Mathews, P. M. (2000). The endosomal–lysosomal system of neurons in Alzheimer’s disease pathogenesis: A review. Neurochemical Research, 25, 1161–1172.

    Article  PubMed  CAS  Google Scholar 

  • Obulesu, M., & Lakshmi, M. J. (2014). Apoptosis in Alzheimer’s disease: an understanding of the physiology, pathology and therapeutic avenues. Neurochemical Research, 39, 2301–2312.

    Article  PubMed  CAS  Google Scholar 

  • Ostadsharif, M., Ghaedi, K., Hossein Nasr-Esfahani, M., Mojbafan, M., Tanhaie, S., Karbalaie, K., & Baharvand, H. (2011). The expression of peroxisomal protein transcripts increased by retinoic acid during neural differentiation. Differentiation, 81, 127–132.

    Article  PubMed  CAS  Google Scholar 

  • Outeiro, T. F., Marques, O., & Kazantsev, A. (2008). Therapeutic role of sirtuins in neurodegenerative disease. Biochimica et Biophysica Acta, 1782, 363–369.

    Article  PubMed  CAS  Google Scholar 

  • Payne, B. A., & Chinnery, P. F. (2015). Mitochondrial dysfunction in aging: Much progress but many unresolved questions. Biochim Biophys Acta, 1847(11), 1347–1353. 

    Article  CAS  Google Scholar 

  • Petzold, A., Psotta, L., Brigadski, T., Endres, T., & Lessmann, V. (2015). Chronic BDNF deficiency leads to an age-dependent impairment in spatial learning. Neurobiology of Learning and Memory, 120, 52–60.

    Article  PubMed  CAS  Google Scholar 

  • Phillips, C., Baktir, M. A., Srivatsan, M., & Salehi, A. (2014). Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Frontiers in Cellular Neuroscience, 8, 170.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Picconi, B., Piccoli, G., & Calabresi, P. (2012). Synaptic dysfunction in Parkinson’s disease. Advances in Experimental Medicine and Biology, 970, 553–572.

    Article  PubMed  CAS  Google Scholar 

  • Picone, P., Nuzzo, D., Caruana, L., Scafidi, V., Di Carlo, M. (2014). Mitochondrial dysfunction: different routes to Alzheimer's disease therapy. Oxid Med Cell Longev, 2014, 780179.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Pizzorusso, T., Ratto, G. M., Putignano, E., & Maffei, L. (2000). Brain-derived neurotrophic factor causes cAMP response element-binding protein phosphorylation in absence of calcium increases in slices and cultured neurons from rat visual cortex. Journal of Neuroscience, 20, 2809–2816.

    PubMed  CAS  Google Scholar 

  • Przedborski, S., Vila, M., & Jackson-Lewis, V. (2003). Neurodegeneration: What is it and where are we? Journal of Clinical Investigation, 111, 3–10.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998). A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 92, 829–839.

    Article  PubMed  CAS  Google Scholar 

  • Qin, W., Haroutunian, V., Katsel, P., Cardozo, C. P., Ho, L., Buxbaum, J. D., & Pasinetti, G. M. (2009). PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Archives of Neurology, 66, 352–361.

    Article  PubMed Central  PubMed  Google Scholar 

  • Qin, W., Yang, T., Ho, L., Zhao, Z., Wang, J., Chen, L., et al. (2006). Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. Journal of Biological Chemistry, 281, 21745–21754.

    Article  PubMed  CAS  Google Scholar 

  • Rabiee, F., Forouzanfar, M., Ghazvini Zadegan, F., Tanhaei, S., Ghaedi, K., Motovali Bashi, M., et al. (2014). Induced expression of Fndc5 significantly increased cardiomyocyte differentiation rate of mouse embryonic stem cells. Gene, 551, 127–137.

    Article  PubMed  CAS  Google Scholar 

  • Radak, Z., Chung, H. Y., & Goto, S. (2005). Exercise and hormesis: Oxidative stress-related adaptation for successful aging. Biogerontology, 6, 71–75.

    Article  PubMed  CAS  Google Scholar 

  • Raschke, S., Elsen, M., Gassenhuber, H., Sommerfeld, M., Schwahn, U., Brockmann, B., et al. (2013). Evidence against a beneficial effect of irisin in humans. PLoS ONE, 8, e73680.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Reddy, P. H. (2009). Role of mitochondria in neurodegenerative diseases: Mitochondria as a therapeutic target in Alzheimer’s disease. CNS Spectrums, 14, 8–13. discussion 16–18.

    PubMed Central  PubMed  Google Scholar 

  • Reichardt, L. F. (2006). Neurotrophin-regulated signalling pathways. Philosophical Transactions of the Royal Society of London. Series B, Biological sciences, 361, 1545–1564.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rinnerthaler, M., Bischof, J., Streubel, M. K., Trost, A., & Richter, K. (2015). Oxidative stress in aging human skin. Biomolecules, 5, 545–589.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rossignol, D. A., & Frye, R. E. (2012). A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Molecular Psychiatry, 17, 389–401.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ruetenik, A., & Barrientos, A. (2015) Dietary restriction, mitochondrial function and aging: From yeast to humans. Biochim Biophys Acta, 1847(11), 1434–1447.

    Article  PubMed  CAS  Google Scholar 

  • Santos, M. J., Quintanilla, R. A., Toro, A., Grandy, R., Dinamarca, M. C., Godoy, J. A., & Inestrosa, N. C. (2005). Peroxisomal proliferation protects from beta-amyloid neurodegeneration. Journal of Biological Chemistry, 280, 41057–41068.

    Article  PubMed  CAS  Google Scholar 

  • Scarpulla, R. C. (2008). Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiological Reviews, 88, 611–638.

    Article  PubMed  CAS  Google Scholar 

  • Schäbitz, W. R., Sommer, C., Zoder, W., Kiessling, M., Schwaninger, M., & Schwab, S. (2000). Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia. Stroke, 31, 2212–2217.

    Article  PubMed  Google Scholar 

  • Schon, E. A., DiMauro, S., Hirano, M., & Gilkerson, R. W. (2010). Therapeutic prospects for mitochondrial disease. Trends in Molecular Medicine, 16, 268–276.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Schreiber, S. N., Emter, R., Hock, M. B., Knutti, D., Cardenas, J., Podvinec, M., et al. (2004). The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis. Proceedings of the National Academy of Sciences USA, 101, 6472–6477.

    Article  CAS  Google Scholar 

  • Selkoe, D. J., & Schenk, D. (2003). Alzheimer’s disease: Molecular understanding predicts amyloid-based therapeutics. Annual Review of Pharmacology and Toxicology, 43, 545–584.

    Article  PubMed  CAS  Google Scholar 

  • Sen, S., Nesse, R. M., Stoltenberg, S. F., Li, S., Gleiberman, L., Chakravarti, A., et al. (2003). A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology, 28, 397–401.

    Article  PubMed  CAS  Google Scholar 

  • Sharon, R., Bar-Joseph, I., Frosch, M. P., Walsh, D. M., Hamilton, J. A., & Selkoe, D. J. (2003a). The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson’s disease. Neuron, 37, 583–595.

    Article  PubMed  CAS  Google Scholar 

  • Sharon, R., Bar-Joseph, I., Mirick, G. E., Serhan, C. N., & Selkoe, D. J. (2003b). Altered fatty acid composition of dopaminergic neurons expressing alpha-synuclein and human brains with alpha-synucleinopathies. Journal of Biological Chemistry, 278, 49874–49881.

    Article  PubMed  CAS  Google Scholar 

  • Sheikh, F. G., Pahan, K., Khan, M., Barbosa, E., & Singh, I. (1998). Abnormality in catalase import into peroxisomes leads to severe neurological disorder. Proceedings of the National Academy of Sciences, 95, 2961–2966.

    Article  CAS  Google Scholar 

  • Sheng, B., Wang, X., Su, B., Lee, H. G., Casadesus, G., Perry, G., & Zhu, X. (2012). Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease. Journal of Neurochemistry, 120, 419–429.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Shin, J. H., Ko, H. S., Kang, H., Lee, Y., Lee, Y. I., Pletinkova, O., et al. (2011). PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson’s disease. Cell, 144, 689–702.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Shutt, T.E.,& McBride, H.M. (2013). Staying cool in difficult times: mitochondrial dynamics, quality control and the stress response. Biochim Biophys Acta, 1833(2), 417–424.

    Article  PubMed  CAS  Google Scholar 

  • Song, W., Chen, J., Petrilli, A., Liot, G., Klinglmayr, E., Zhou, Y., et al. (2011). Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nature Medicine, 17, 377–382.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Spiegelman, B. M. (2013). Banting Lecture 2012 Regulation of adipogenesis: Toward new therapeutics for metabolic disease. Diabetes, 62, 1774–1782.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Steinberg, S. J., Dodt, G., Raymond, G. V., Braverman, N. E., Moser, A. B., & Moser, H. W. (2006). Peroxisome biogenesis disorders. Biochimica et Biophysica Acta, 1763, 1733–1748.

    Article  PubMed  CAS  Google Scholar 

  • St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., et al. (2006). Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell, 127, 397–408.

    Article  PubMed  CAS  Google Scholar 

  • Sun, M., Kong, L., Wang, X., Lu, X. G., Gao, Q., & Geller, A. I. (2005). Comparison of the capability of GDNF, BDNF, or both, to protect nigrostriatal neurons in a rat model of Parkinson’s disease. Brain Research, 1052, 119–129.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Tapia-Arancibia, L., Aliaga, E., Silhol, M., & Arancibia, S. (2008). New insights into brain BDNF function in normal aging and Alzheimer disease. Brain Research Reviews, 59, 201–220.

    Article  PubMed  CAS  Google Scholar 

  • Tapia-Arancibia, L., Rage, F., Givalois, L., & Arancibia, S. (2004). Physiology of BDNF: Focus on hypothalamic function. Frontiers in Neuroendocrinology, 25, 77–107.

    Article  PubMed  CAS  Google Scholar 

  • Tillement, L., Lecanu, L., & Papadopoulos, V. (2011). Alzheimer’s disease: Effects of β-amyloid on mitochondria. Mitochondrion, 11, 13–21.

    Article  PubMed  CAS  Google Scholar 

  • Tong, L., Balazs, R., Thornton, P. L., & Cotman, C. W. (2004). Beta-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons. Journal of Neuroscience, 24, 6799–6809.

    Article  PubMed  CAS  Google Scholar 

  • Trempe, J.F., & Fon, E.A. (2013). Structure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection. Front Neurol, 4, 38.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Tretter, L., Sipos, I., & Adam-Vizi, V. (2004). Initiation of neuronal damage by complex I deficiency and oxidative stress in Parkinson’s disease. Neurochemical Research, 29, 569–577.

    Article  PubMed  CAS  Google Scholar 

  • Tsai, S. J. (2006). TrkB partial agonists: potential treatment strategy for epilepsy, mania, and autism. Medical Hypotheses, 66, 173–175.

    Article  PubMed  CAS  Google Scholar 

  • Tsunemi, T., Ashe, T. D., Morrison, B. E., Soriano, K. R., Au, J., Roque, R. A., et al. (2012). PGC-1α rescues Huntington’s disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Science Translational Medicine, 4, 142ra197.

    Article  CAS  Google Scholar 

  • van der Valk, P., Gille, J. J., Oostra, A. B., Roubos, E. W., Sminia, T., & Joenje, H. (1985). Characterization of an oxygen-tolerant cell line derived from Chinese hamster ovary. Antioxygenic enzyme levels and ultrastructural morphometry of peroxisomes and mitochondria. Cell and Tissue Research, 239, 61–68.

    Article  PubMed  Google Scholar 

  • Vega, R. B., Huss, J. M., & Kelly, D. P. (2000). The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Molecular and Cellular Biology, 20, 1868–1876.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ventriglia, M., Bocchio Chiavetto, L., Benussi, L., Binetti, G., Zanetti, O., Riva, M. A., & Gennarelli, M. (2002). Association between the BDNF 196 A/G polymorphism and sporadic Alzheimer’s disease. Molecular Psychiatry, 7, 136–137.

    Article  PubMed  CAS  Google Scholar 

  • Vila, M., & Przedborski, S. (2003). Targeting programmed cell death in neurodegenerative diseases. Nature Reviews Neuroscience, 4, 365–375.

    Article  PubMed  CAS  Google Scholar 

  • Villena, J. A. (2015). New insights into PGC-1 coactivators: redefining their role in the regulation of mitochondrial function and beyond. FEBS Journal, 282, 647–672.

    Article  PubMed  CAS  Google Scholar 

  • Volakakis, N., Kadkhodaei, B., Joodmardi, E., Wallis, K., Panman, L., Silvaggi, J., et al. (2010). NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection. Proceedings of the National Academy of Sciences USA, 107, 12317–12322.

    Article  CAS  Google Scholar 

  • Wallace, D. C., & Fan, W. (2009). The pathophysiology of mitochondrial disease as modeled in the mouse. Genes and Development, 23, 1714–1736.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wanders, R. J., & Waterham, H. R. (2005). Peroxisomal disorders I: Biochemistry and genetics of peroxisome biogenesis disorders. Clinical Genetics, 67, 107–133.

    Article  PubMed  CAS  Google Scholar 

  • Wanders, R. J., & Waterham, H. R. (2006). Peroxisomal disorders: The single peroxisomal enzyme deficiencies. Biochimica et Biophysica Acta, 1763, 1707–1720.

    Article  PubMed  CAS  Google Scholar 

  • Wang, R., Li, J. J., Diao, S., Kwak, Y. D., Liu, L., Zhi, L., et al. (2013). Metabolic stress modulates Alzheimer’s β-secretase gene transcription via SIRT1-PPARγ-PGC-1 in neurons. Cell Metabolism, 17, 685–694.

    Article  PubMed  CAS  Google Scholar 

  • Wenz, T. (2009). PGC-1alpha activation as a therapeutic approach in mitochondrial disease. IUBMB Life, 61, 1051–1062.

    Article  PubMed  CAS  Google Scholar 

  • Wenz, T. (2011). Mitochondria and PGC-1α in aging and age-associated diseases. Journal of Aging Research, 2011, 810619.

    Article  PubMed Central  PubMed  Google Scholar 

  • West, A. P., Shadel, G. S., & Ghosh, S. (2011). Mitochondria in innate immune responses. Nature Reviews Immunology, 11, 389–402.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Weydt, P., Soyal, S. M., Gellera, C., Didonato, S., Weidinger, C., Oberkofler, H., et al. (2009). The gene coding for PGC-1alpha modifies age at onset in Huntington’s Disease. Molecular neurodegeneration, 4, 3.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Winterbourn, C. C. (1995). Toxicity of iron and hydrogen peroxide: The Fenton reaction. Toxicology Letters, 82–83, 969–974.

    Article  PubMed  Google Scholar 

  • Witte, M. E., Geurts, J. J., de Vries, H. E., van der Valk, P., & van Horssen, J. (2010). Mitochondrial dysfunction: A potential link between neuroinflammation and neurodegeneration? Mitochondrion, 10, 411–418.

    Article  PubMed  CAS  Google Scholar 

  • Wood, C. S., Koepke, J. I., Teng, H., Boucher, K. K., Katz, S., Chang, P., et al. (2006). Hypocatalasemic fibroblasts accumulate hydrogen peroxide and display age-associated pathologies. Traffic, 7, 97–107.

    Article  PubMed  CAS  Google Scholar 

  • Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., et al. (2013). Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metabolism, 18, 649–659.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wu, Z., Huang, X., Feng, Y., Handschin, C., Gullicksen, P. S., Bare, O., et al. (2006). Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha transcription and mitochondrial biogenesis in muscle cells. Proceedings of the National Academy of Sciences USA, 103, 14379–14384.

    Article  CAS  Google Scholar 

  • Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., et al. (1999). Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell, 98, 115–124.

    Article  PubMed  CAS  Google Scholar 

  • Yakunin, E., Moser, A., Loeb, V., Saada, A., Faust, P., Crane, D. I., et al. (2010). alpha-Synuclein abnormalities in mouse models of peroxisome biogenesis disorders. Journal of Neuroscience Research, 88, 866–876.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Yang, L., Long, Q., Liu, J., Tang, H., Li, Y., Bao, F., Qin, D., Pei, D., Liu, X. (2015). Mitochondrial fusion provides an ‘initial metabolic complementation’ controlled by mtDNA. Cell Mol Life Sci, 72(13):2585-2598.

    Article  PubMed  CAS  Google Scholar 

  • Yu, S. P. (2003). Na(+), K(+)-ATPase: the new face of an old player in pathogenesis and apoptotic/hybrid cell death. Biochemical Pharmacology, 66, 1601–1609.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y., Ma, K., Song, S., Elam, M. B., Cook, G. A., & Park, E. A. (2004). Peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) enhances the thyroid hormone induction of carnitine palmitoyltransferase I (CPT-I alpha). Journal of Biological Chemistry, 279, 53963–53971.

    Article  PubMed  CAS  Google Scholar 

  • Zhao, W., Varghese, M., Yemul, S., Pan, Y., Cheng, A., Marano, P., et al. (2011). Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1α) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis. Molecular Neurodegeneration, 6, 51.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zheng, B., Liao, Z., Locascio, J. J., Lesniak, K. A., Roderick, S. S., Watt, M. L., et al. (2010). PGC-1α, a potential therapeutic target for early intervention in Parkinson’s disease. Science Translational Medicine, 2, 52ra73.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zorzano, A., & Claret, M. (2015). Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction. Front Aging Neurosci, 7, 101.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all of our colleagues at the Royan Institute for Biotechnology who contributed to the work discussed in this review.

Author information

Authors and Affiliations

  1. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Royan Street, Salman Street, Khorasgan, Isfahan, 8165131378, Iran

    Mohammad Jodeiri Farshbaf, Kamran Ghaedi & Mohammad Hossein Nasr-Esfahani

  2. Department of Biology, School of Sciences, University of Isfahan, Hezarjerib Street, Azadi Square, Isfahan, 8174673441, Iran

    Mohammad Jodeiri Farshbaf, Kamran Ghaedi & Mahsa Shirani Faradonbeh

  3. Department of Biology, New Mexico State University, Las Cruces, NM, USA

    Mohammad Jodeiri Farshbaf, Jennifer Curtiss & Pooneh Vaziri

  4. Department of Biomedical Sciences, Florida State University College of Medicine, West Call Street, Tallahassee, FL, 32306-4300, USA

    Timothy L. Megraw

Authors
  1. Mohammad Jodeiri Farshbaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kamran Ghaedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Timothy L. Megraw
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jennifer Curtiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mahsa Shirani Faradonbeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pooneh Vaziri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohammad Hossein Nasr-Esfahani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kamran Ghaedi, Timothy L. Megraw or Mohammad Hossein Nasr-Esfahani.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jodeiri Farshbaf, M., Ghaedi, K., Megraw, T.L. et al. Does PGC1α/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders?. Neuromol Med 18, 1–15 (2016). https://doi.org/10.1007/s12017-015-8370-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12017-015-8370-x

Keywords

Search

Navigation