New therapies on the horizon: Targeted protein degradation in neuroscience

Cell Chem Biol. 2024 Sep 19;31(9):1688-1698. doi: 10.1016/j.chembiol.2024.08.010.

Abstract

This minireview explores the burgeoning field of targeted protein degradation (TPD) and its promising applications in neuroscience and clinical development. TPD offers innovative strategies for modulating protein levels, presenting a paradigm shift in small-molecule drug discovery and therapeutic interventions. Importantly, small-molecule protein degraders specifically target and remove pathogenic proteins from central nervous system cells without the drug delivery challenges of genomic and antibody-based modalities. Here, we review recent advancements in TPD technologies, highlight proteolysis targeting chimera (PROTAC) protein degrader molecules with proximity-induced degradation event-driven and iterative pharmacology, provide applications in neuroscience research, and discuss the high potential for translation of TPD into clinical settings.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery
  • Humans
  • Neurosciences
  • Proteolysis* / drug effects
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology

Substances

  • Small Molecule Libraries