Expanding insights on the involvement of endoplasmic reticulum stress in Parkinson's disease.
Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by selective loss of dopaminergic neurons and the presence of Lewy bodies. The pathogenesis of PD remains incompletely understood. Environmental factors, oxidative damage, misfolded protein aggregates, ubiquitin-proteasome system impairment, and mitochondrial dysfunction might all be involved. Recent studies point to activation of endoplasmic reticulum (ER) stress-mediated cell death linked to PD. Accumulation of unfolded and/or misfolded proteins in the ER lumen induces ER stress. To withstand such potentially lethal conditions, intracellular signaling pathways collectively termed the unfolded protein responses (UPR) are activated. The UPR include translational attenuation, induction of ER resident chaperones, and degradation of misfolded proteins through the ER-associated degradation. In case of severe and/or prolonged ER stress, cellular signals leading to cell death are activated. Accumulating evidence suggests that ER stress induced by aberrant protein degradation is implicated in PD. Here the authors review the emerging role of ER stress in PD and related disorders, and highlight current knowledge in this field that may reveal novel insight into disease mechanisms and help to provide novel avenues to potential therapies.
Wang
Hua-Qin
HQ
Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takahashi
Ryosuke
R
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D014118:Toxins, Biological / Q000633:toxicity; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
C480827:GPR37 receptor, human; D043562:Receptors, G-Protein-Coupled; D014118:Toxins, Biological; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein