Synucleins: New Data on Misfolding, Aggregation and Role in Diseases

Biomedicines. 2022 Dec 13;10(12):3241. doi: 10.3390/biomedicines10123241.

Abstract

The synucleins are a family of natively unfolded (or intrinsically unstructured) proteins consisting of α-, β-, and γ-synuclein involved in neurodegenerative diseases and cancer. The current number of publications on synucleins has exceeded 16.000. They remain the subject of constant interest for over 35 years. Two reasons explain this unchanging attention: synuclein's association with several severe human diseases and the lack of understanding of the functional roles under normal physiological conditions. We analyzed recent publications to look at the main trends and developments in synuclein research and discuss possible future directions. Traditional areas of peak research interest which still remain high among last year's publications are comparative studies of structural features as well as functional research on of three members of the synuclein family. Another popular research topic in the area is a mechanism of α-synuclein accumulation, aggregation, and fibrillation. Exciting fast-growing area of recent research is α-synuclein and epigenetics. We do not present here a broad and comprehensive review of all directions of studies but summarize only the most significant recent findings relevant to these topics and outline potential future directions.

Keywords: Parkinson’s disease; SNARE-complex; epigenetic; histones; methylation; phytochemicals; protein aggregation; protein trafficking; synucleinopathies; α-, β- and γ-synuclein.

Publication types

  • Review

Grants and funding

Some of the work by A.S. (Andrei Surguchov) was conducted at the Kansas City VA Medical Center, Kansas City, MO, United States, with support from VA Merit Review grants 1I01BX000361 and the Glaucoma Foundation grant QB42308. A.S. (Alexei Surguchev) is partially supported by YALE ENT Research grant # YD000220. The authors would like to thank Marina Nikolaev for advice and technical assistance with illustrations.