title: Targeting chaperones, heat shock factor-1, and unfolded protein response: Promising therapeutic approaches for neurodegenerative disorders.
abstract: Protein misfolding, which is known to cause several serious diseases, is an emerging field that addresses multiple therapeutic areas. Misfolding of a disease-specific protein in the central nervous system ultimately results in the formation of toxic aggregates that may accumulate in the brain, leading to neuronal cell death and dysfunction, and associated clinical manifestations. A large number of neurodegenerative diseases in humans, including Alzheimer's, Parkinson's, Huntington's, and prion diseases, are primarily caused by protein misfolding and aggregation. Notably, the cellular system is equipped with a protein quality control system encompassing chaperones, ubiquitin proteasome system, and autophagy, as a defense mechanism that monitors protein folding and eliminates inappropriately folded proteins. As the intrinsic molecular mechanisms of protein misfolding become more clearly understood, the novel therapeutic approaches in this arena are gaining considerable interest. The present review will describe the chaperones network and different approaches as the therapeutic targets for neurodegenerative diseases. Current and emerging therapeutic approaches to combat neurodegenerative diseases, addressing the roles of molecular, chemical, and pharmacological chaperones, as well as heat shock factor-1 and the unfolded protein response, are also discussed in detail.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Shambhunath
authors.initials: S
authors.lastname: Bose
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Republic of Korea. Electronic address: neuroph@dongguk.edu.
authors.forename: Jungsook
authors.initials: J
authors.lastname: Cho
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D001921:Brain / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D018832:Molecular Chaperones; D046988:Proteasome Endopeptidase Complex
keywords: Heat shock factor-1; Molecular chaperones; Neurodegenerative disorders; Protein misfolding; Protein quality control system; Unfolded protein response