Development of a hydroxyflavone-labelled 4554W peptide probe for monitoring αS aggregation

Sci Rep. 2023 Jul 6;13(1):10968. doi: 10.1038/s41598-023-37655-3.

Abstract

Parkinson's is the second most common neurodegenerative disease, with the number of individuals susceptible due to increase as a result of increasing life expectancy and a growing worldwide population. However, despite the number of individuals affected, all current treatments for PD are symptomatic-they alleviate symptoms, but do not slow disease progression. A major reason for the lack of disease-modifying treatments is that there are currently no methods to diagnose individuals during the earliest stages of the disease, nor are there any methods to monitor disease progression at a biochemical level. Herein, we have designed and evaluated a peptide-based probe to monitor αS aggregation, with a particular focus on the earliest stages of the aggregation process and the formation of oligomers. We have identified the peptide-probe K1 as being suitable for further development to be applied to number of applications including: inhibition of αS aggregation; as a probe to monitor αS aggregation, particularly at the earliest stages before Thioflavin-T is active; and a method to detect early-oligomers. With further development and in vivo validation, we anticipate this probe could be used for the early diagnosis of PD, a method to evaluate the effectiveness of potential therapeutics, and as a tool to help in the understanding of the onset and development of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Neurodegenerative Diseases*
  • Peptides
  • alpha-Synuclein

Substances

  • alpha-Synuclein
  • Peptides