PROTAC-Based Therapeutics: From Design to Clinical Potential in Neurodegenerative Disease - PubMed
4 hours ago
- #protein-degradation
- #neurodegenerative-diseases
- #PROTACs
- Neurodegenerative diseases like Alzheimer's, Parkinson's, and ALS involve misfolded and aggregated proteins.
- Current therapies show modest benefits due to issues like low BBB permeability and inability to clear neuronal proteins.
- PROTACs (proteolysis-targeting chimaeras) are a novel therapeutic strategy that uses the ubiquitin-proteasome system to degrade target proteins.
- PROTACs consist of a target protein ligand, a linker, and an E3 ligase-recruiting ligand, enabling catalytic protein degradation.
- Preclinical studies highlight PROTACs' potential in targeting pathological proteins like tau, α-synuclein, TDP-43, and mHTT.
- Advances in brain-permeable PROTACs, E3 ligase expression studies, and iPSC-derived neurons are accelerating progress.
- Despite challenges like pharmacokinetic modifications, PROTACs show major therapeutic promise for neurodegenerative diseases.