The Strategies of Development of New Non-Toxic Inhibitors of Amyloid Formation

Int J Mol Sci. 2023 Feb 14;24(4):3781. doi: 10.3390/ijms24043781.

Abstract

In recent years, due to the aging of the population and the development of diagnostic medicine, the number of identified diseases associated with the accumulation of amyloid proteins has increased. Some of these proteins are known to cause a number of degenerative diseases in humans, such as amyloid-beta (Aβ) in Alzheimer's disease (AD), α-synuclein in Parkinson's disease (PD), and insulin and its analogues in insulin-derived amyloidosis. In this regard, it is important to develop strategies for the search and development of effective inhibitors of amyloid formation. Many studies have been carried out aimed at elucidating the mechanisms of amyloid aggregation of proteins and peptides. This review focuses on three amyloidogenic peptides and proteins-Aβ, α-synuclein, and insulin-for which we will consider amyloid fibril formation mechanisms and analyze existing and prospective strategies for the development of effective and non-toxic inhibitors of amyloid formation. The development of non-toxic inhibitors of amyloid will allow them to be used more effectively for the treatment of diseases associated with amyloid.

Keywords: Alzheimer’s disease; Parkinson’s disease; amyloid; amyloid-beta; diabetes; insulin; α-synuclein.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloidogenic Proteins
  • Humans
  • Insulins*
  • Prospective Studies
  • alpha-Synuclein / metabolism

Substances

  • alpha-Synuclein
  • Amyloid
  • Amyloid beta-Peptides
  • Amyloidogenic Proteins
  • Insulins

Grants and funding

The work was carried out with the financial support of the State Program, (No. 0115-2019-0004).