Scientific Reports (Jul 2023)

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

  • Kathryn J. C. Watt,
  • Richard M. Meade,
  • Tony D. James,
  • Jody M. Mason

DOI
https://doi.org/10.1038/s41598-023-37655-3
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 8

Abstract

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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.