title: Expanding role of molecular chaperones in regulating α-synuclein misfolding; implications in Parkinson's disease.
abstract: Protein misfolding under stressful environmental conditions cause several cellular problems owing to the disturbed cellular protein homeostasis, which may further lead to neurological disorders like Parkinson's disease (PD), Alzheimer's disease (AD), Amyloid lateral sclerosis and Huntington disease (HD). The presence of cellular defense mechanisms like molecular chaperones and proteasomal degradation systems prevent protein misfolding and aggregation. Molecular chaperones plays primary role in preventing protein misfolding by mediating proper native folding, unfolding and refolding of the polypeptides along with vast number of cellular functions. In past few years, the understanding of molecular chaperone mechanisms has been expanded enormously although implementation to prevent protein aggregation diseases is still deficient. We in this review evaluated major classes of molecular chaperones and their mechanisms relevant for preventing protein aggregation, specific case of α-synuclein aggregation. We also evaluate the molecular chaperone function as a novel therapeutic approach and the chaperone inhibitors or activators as small molecular drug targets.
authors: Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, 226001, Uttar Pradesh, India.|Nanotherapeutics and Nanomaterial Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, 226001, Uttar Pradesh, India.
authors: Sandeep K
authors: SK
authors: Sharma
authors: Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, 226001, Uttar Pradesh, India. spriya@iitr.res.in.
authors: Smriti
authors: 0000-0002-3858-9207
authors: S
authors: Priya
mesh_terms: D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D066263:Protein Aggregation, Pathological / Q000378:metabolism* / Q000473:pathology; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D006360:Heat-Shock Proteins; D051844:alpha-Synuclein
keywords: Hsp100; Hsp110; Hsp70; Molecular chaperones; Parkinson’s disease; Protein homeostasis; Small Hsps; α-Synuclein