PROTAC a-Synuclein/Tau degrader 1 is a blood-brain barrier-penetrant dual PROTAC degrader of a-synuclein (a-Syn) and tau, with DC50 of 1.57 µM and 4.09 µM, respectively. PROTAC a-Synuclein/Tau degrader 1 binds to a-Syn and tau PFF, with KDs of 0.47 and 2.78 µM, respectively. PROTAC a-Synuclein/Tau degrader 1 exhibits degradation effect mediated by the ubiquitin-proteasome system (UPS). PROTAC a-Synuclein/Tau degrader 6 can be used for the study of Parkinson’s disease (PD)
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