Fibroblast growth factor 21 and autophagy: A complex interplay in Parkinson disease - 30/05/20
, Sarathlal K C a , Ruei-Dun Tang b , Chih Hao Yang b , Sunil Kumar Dubey a , Rajeev Taliyan a, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Graphical abstract |
Highlights |
• | Parkinson disease (PD) is characterized by a loss of dopaminergic neurones in the substantia nigra pars compacta. |
• | Fibroblast growth factor 21 (FGF21) is a metabolic hormone recently identified as a potent neuroprotective agent. |
• | Impairment of autophagy due to factors like ageing elevates accumulation of misfolded proteins contributing towards possible neurodegenerative pathology. |
• | Autophagy dysfunction causes endoplasmic reticulum (ER) stress that may stimulate the Activating Transcription Factor 4 (ATF 4) which help in preserving neuronal survival and health. |
• | ATF 4 regulates FGF21 expression during ER stress that may promotes neuroprotection in PD through FGF21 mediated mechanism (s). |
Abstract |
Parkinson disease (PD) is the second common neurodegenerative disorder after Alzheimer’s disease (AD). The predominant pathological hallmark is progressive loss of dopaminergic (DA) neurones in the substantia nigra (SN) complicated by aggregation of misfolded forms of alpha-synuclein (α-syn). α-syn is a cytosolic synaptic protein localized in the presynaptic neuron under normal circumstances. What drives misfolding of this protein is largely unknown. However, recent studies suggest that autophagy might be an important risk factor for contributing towards PD. Autophagy is an evolutionarily conserved mechanism that causes the clearance or degradation of misfolded, mutated and damaged proteins, organelles etc. However, in an aging individual this process might deteriorate which could possibly lead to the accumulation of damaged proteins. Hence, autophagy modulation might provide some interesting cues for the treatment of PD. Additionally, Fibroblast growth factor 21 (FGF21) which is known for its role as a potent regulator of glucose and energy metabolism has also proved to be neuroprotective in various neurodegenerative conditions possibly via mediation of autophagy.
Le texte complet de cet article est disponible en PDF.Abbreviations : AD, AKT, ALS, ATF, ATG, ATP, BAT, BBB, CHOP, ChREBP, CMA, CNS, CREBH, CSF, DA, DJ-1, ELF2-α, ER, FGF21, FGFR1, FRS2α, FXR, GR, HIF-1, ICV, iPSC, IRE, ISR, LAMP-2A, LB, LC3, LN, LRRK2, LXR, MAPK, MPP+, mRNA, mtDNA, mTORC1, NAFLD, ORF, PD, PDD, PERK, PINK-1, PPARγ, Rab, RARβ, REM, ROR, siRNA, SN, SNCA, UPR, UPRmt, UPS, UTR, Vps35, WAT, α-syn, β-Klotho
Keywords : Parkinson disease, Fibroblast growth factor 21, Autophagy, Alpha-synuclein
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Vol 127
Article 110145- juillet 2020 Retour au numéro
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