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Advanced Neurology Brain bioavailability of targeted protein degraders

References 85 86 4 87

Structure

E3 ligase ligand CRBN; VHL CRBN VHL CRBN Abbreviations: CRBN: Cereblon; GSK-3β: Glycogen synthase kinase-3 beta; LRRK2: Leucine-rich repeat kinase; TDP-43: Transactive response DNA binding protein 43 kDa; TPD: Targeted protein

Targeted protein α-synuclein GSK-3β LRRK2 TDP-43

Development stage Preclinical Preclinical Preclinical Preclinical

Indication Parkinson’s disease; α-synucleinopathies GSK-3β degradation Parkinson’s disease Amyotrophic lateral sclerosis; TDP-43

Table 2. (Continued) TPD α-Synuclein Degrader PG-21 XL01126 JMF4560 degraders; VHL: Von Hippel–Lindau.

Volume 4 Issue 2 (2025) 62 doi: 10.36922/an.5140