PROTAC-mediated multi-target protein degradation in Alzheimer's disease: mechanistic insights, therapeutic applications, and translational challenges
Bin Wang, Yunan Li, Tingting Yao, Xinai Shen, Huan Li, Wei Jiang, Xinuo Li, Zheying Zhu
TL;DR
This paper explores how PROTAC technology can degrade harmful proteins in Alzheimer's disease, offering a promising alternative to current therapies.
Contribution
The paper provides mechanistic insights and therapeutic applications of PROTACs for targeting multiple proteins in Alzheimer's.
Findings
PROTACs can selectively degrade intracellular pathogenic proteins in Alzheimer's.
Current therapies have limitations like immune dependency and poor intracellular access.
PROTACs offer a new approach by leveraging the ubiquitin–proteasome system for efficient protein clearance.
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by multiple interacting pathological mechanisms. Among these, the core driving factor is the accumulation of abnormally folded, neurotoxic proteins. Current therapeutic options, particularly immunotherapies, remain limited due to their reliance on immune-mediated clearance, the need for high-dose administration, and their inability to access intracellular targets, making them less patient-friendly and therapeutically efficient. This is precisely where proteolysis-targeting chimera (PROTAC) technology offers a transformative advantage. By harnessing the ubiquitin–proteasome system (UPS), PROTACs can selectively recruit degradation machinery to target proteins, thereby facilitating their ubiquitination and subsequent clearance. This mechanism allows PROTACs to efficiently eliminate pathogenic proteins while…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
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Taxonomy
TopicsProtein Degradation and Inhibitors · Histone Deacetylase Inhibitors Research · 14-3-3 protein interactions