title: Targeting oligomers in neurodegenerative disorders: lessons from α-synuclein, tau, and amyloid-β peptide.
abstract: Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Prion disease, Huntington's disease, and amyotrophic lateral sclerosis are increasingly being realized to have common cellular and molecular mechanisms including protein aggregation and inclusion body formation in selected brain regions. The aggregates usually consist of insoluble fibrillar aggregates containing misfolded protein with β-sheet conformation. The most probable explanation is that inclusions and the aggregates symbolize an end stage of a molecular cascade of several events, and that earlier event in the cascade may be more directly tied up to pathogenesis than the inclusions themselves. Small intermediates termed as 'soluble oligomers' in the aggregation process might influence synaptic dysfunction, whereas large, insoluble deposits might function as reservoir of the bioactive oligomers. Compelling evidence suggests the role of misfolded proteins in the form of oligomers might lead to synaptic dysfunction, neuronal apoptosis and brain damage. However, the mechanism by which oligomers trigger neurodegeneration still remains mysterious. The aim of this article is to review the literature around the molecular mechanism and role of oligomers in neurodegeneration and leading approaches toward rational therapeutics.
authors: Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, TX 75390-9070, USA. b4utsw@gmail.com
authors: Bharathi Shrikanth
authors: BS
authors: Gadad
authors: Gabrielle B
authors: GB
authors: Britton
authors: K S
authors: KS
authors: Rao
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000628:therapy*; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins