Development of a targeted BioPROTAC degrader selective for misfolded SOD1 | Nature Communications
Conventional PROTACs have limited capacity for misfolded proteins. Here, authors develop a BioPROTAC containing an scFv specifically targeting misfolded SOD1, fused to an E3 ligase, and demonstrate a strategy for reducing misfolded SOD1 accumulation.
Introduction Targeted protein degradation (TPD) is an emerging therapeutic strategy that leverages endogenous protein quality control systems to selectively degrade disease-associated proteins. TPD utilises bifunctional molecules in an induced proximity approach1, which brings together target proteins and key players in the ubiquitin proteasome (UPS) or the lysosomal autophagy degradation pathways, to degrade target proteins2. The induced proximity strategy has the potential to revolutionise the treatment of neurodegenerative diseases characterised by the accumulation of misfolded or toxic…
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