Targeted degradation of ⍺-synuclein aggregates in Parkinson's disease using the AUTOTAC technology.

ABSTRACT:

Background

There are currently no disease-modifying therapeutics for Parkinson's disease (PD). Although extensive efforts were undertaken to develop therapeutic approaches to delay the symptoms of PD, untreated α-synuclein (α-syn) aggregates cause cellular toxicity and stimulate further disease progression. PROTAC (Proteolysis-Targeting Chimera) has drawn attention as a therapeutic modality to target α-syn. However, no PROTACs have yet shown to selectively degrade α-syn aggregates mainly owing to the limited capacity of the proteasome to degrade aggregates, necessitating the development of novel approaches to fundamentally eliminate α-syn aggregates.

Methods

We employed AUTOTAC (Autophagy-Targeting Chimera), a macroautophagy-based targeted protein degradation (TPD) platform

SUBMITTER: Lee J 

PROVIDER: S-EPMC10290391 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature