Inhibiting toxic aggregation of amyloidogenic proteins: A therapeutic strategy for protein misfolding diseases |
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Authors: | Biao Cheng Hao Gong Hongwen Xiao Robert B Petersen Ling Zheng Kun Huang |
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Institution: | 1. Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, PR China;2. China Institute of Atomic Energy, P. O. Box 275-30, Beijing 102413, PR China;3. Departments of Pathology, Neuroscience and Neurology, Case Western Reserve University, Cleveland, OH 44106, USA;4. College of Life Sciences, Wuhan University, Wuhan 430072, PR China;5. Centre for Biomedicine Research, Wuhan Institutes of Biotechnology, Wuhan 430074, PR China |
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Abstract: | BackgroundThe deposition of self-assembled amyloidogenic proteins is associated with multiple diseases, including Alzheimer's disease, Parkinson's disease and type 2 diabetes mellitus. The toxic misfolding and self-assembling of amyloidogenic proteins are believed to underlie protein misfolding diseases. Novel drug candidates targeting self-assembled amyloidogenic proteins represent a potential therapeutic approach for protein misfolding diseases.Scope of reviewIn this perspective review, we provide an overview of the recent progress in identifying inhibitors that block the aggregation of amyloidogenic proteins and the clinical applications thereof.Major conclusionsCompounds such as polyphenols, certain short peptides, and monomer- or oligomer-specific antibodies, can interfere with the self-assembly of amyloidogenic proteins, prevent the formation of oligomers, amyloid fibrils and the consequent cytotoxicity.General significanceSome inhibitors have been tested in clinical trials for treating protein misfolding diseases. Inhibitors that target the aggregation of amyloidogenic proteins bring new hope to therapy for protein misfolding diseases. |
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Keywords: | AChE acetylcholinesterase AD Alzheimer's disease AIF apoptosis induce factor Aβ amyloid-beta BBB blood brain barrier CA caffeic acid CD circular dichroism CGA chlorogenic acid CNS central nervous system CHOP C/EBP Homologous Protein EGCG (&minus )-epigallocatechin 3-gallate ER endoplasmic reticulum FAP familial amyloid polyneuropathy HD Huntington disease Htt huntingtin PD Parkinson's disease PICUP photo-induced cross-linking of unmodified proteins PMDs protein misfolding diseases ROS reactive oxygen species SAR structure&ndash activity relationships T2DM type 2 diabetes mellitus |
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