Advancements in PROTAC-based therapies for neurodegenerative diseases

Neurodegenerative diseases are characterized by impairments in movement and cognitive functions. These disorders are frequently associated with the accumulation of misfolded protein aggregates, which present significant challenges for treatment with conventional small-molecule inhibitors. While FDA-approved amyloid-beta-directed antibodies, such as Lecanemab, have recently shown clinical success in modifying disease progression, there are currently no treatments capable of curing neurodegenerative diseases. Emerging technologies like proteolysis-targeting chimeras (PROTACs) offer additional promise by targeting disease-causing proteins for degradation, potentially opening new therapeutic avenues. Recent experiments have demonstrated that PROTACs can specifically target and degrade pathogenic proteins associated with neurodegenerative diseases, thereby offering potential therapeutic avenues. This review discusses the latest advances in employing PROTACs for treating neurodegenerative diseases and delves into the associated challenges and opportunities. Our goal is to provide researchers in drug development with new insights on creating novel PROTACs for therapeutic applications.