title: Does PGC1α/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders?
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.
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Royan Street, Salman Street, Khorasgan, Isfahan, 8165131378, Iran.|Department of Biology, School of Sciences, University of Isfahan, Hezarjerib Street, Azadi Square, Isfahan, 8174673441, Iran.|Department of Biology, New Mexico State University, Las Cruces, NM, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jodeiri Farshbaf
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Royan Street, Salman Street, Khorasgan, Isfahan, 8165131378, Iran. kamranghaedi@royaninstitute.org.|Department of Biology, School of Sciences, University of Isfahan, Hezarjerib Street, Azadi Square, Isfahan, 8174673441, Iran. kamranghaedi@royaninstitute.org.
authors.forename: Kamran
authors.initials: K
authors.lastname: Ghaedi
authors.affiliation: Department of Biomedical Sciences, Florida State University College of Medicine, West Call Street, Tallahassee, FL, 32306-4300, USA. timothy.megraw@med.fsu.edu.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Megraw
authors.affiliation: Department of Biology, New Mexico State University, Las Cruces, NM, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Curtiss
authors.affiliation: Department of Biology, School of Sciences, University of Isfahan, Hezarjerib Street, Azadi Square, Isfahan, 8174673441, Iran.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Shirani Faradonbeh
authors.affiliation: Department of Biology, New Mexico State University, Las Cruces, NM, USA.
authors.forename: Pooneh
authors.initials: P
authors.lastname: Vaziri
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Royan Street, Salman Street, Khorasgan, Isfahan, 8165131378, Iran. mh_nasr@royaninstitute.org.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Nasr-Esfahani
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D005081:Exercise Therapy; D025461:Feedback, Physiological; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000502:physiology; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology / Q000517:prevention & control*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D001678:Organelle Biogenesis; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000502:physiology*; D020675:Peroxisomes / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C115163:CREB1 protein, human; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C577593:FNDC5 protein, human; C571428:FNDC5 protein, mouse; D005353:Fibronectins; D009419:Nerve Tissue Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C579455:BDNF protein, human
keywords: BDNF; FNDC5; Irisin; Neurodegenerative diseases; Neuroprotection; PGC1α