Inhibiting toxic aggregation of amyloidogenic proteins: a therapeutic strategy for protein misfolding diseases
- PMID: 23820032
- DOI: 10.1016/j.bbagen.2013.06.029
Inhibiting toxic aggregation of amyloidogenic proteins: a therapeutic strategy for protein misfolding diseases
Abstract
Background: The 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 review: In 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 conclusions: Compounds 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 significance: Some 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.
Keywords: (−)-epigallocatechin 3-gallate; AChE; AD; AIF; Alzheimer's disease; Amyloid; Aβ; BBB; C/EBP Homologous Protein; CA; CD; CGA; CHOP; CNS; Cytotoxicity; EGCG; ER; FAP; HD; Htt; Huntington disease; Inhibitor; PD; PICUP; PMDs; Parkinson's disease; Polyphenols; Protein misfolding disease; ROS; SAR; T2DM; acetylcholinesterase; amyloid-beta; apoptosis induce factor; blood brain barrier; caffeic acid; central nervous system; chlorogenic acid; circular dichroism; endoplasmic reticulum; familial amyloid polyneuropathy; huntingtin; photo-induced cross-linking of unmodified proteins; protein misfolding diseases; reactive oxygen species; structure–activity relationships; type 2 diabetes mellitus.
© 2013.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous