Gene-modified animal models of Parkinson's disease

Exp Neurol. 2025 Aug:390:115287. doi: 10.1016/j.expneurol.2025.115287. Epub 2025 May 4.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that commonly occurs in older individuals and clinically manifests as resting tremors, bradykinesia, muscle stiffness, and impaired postural balance. From a genetic perspective, animal models using gene-editing technologies offer distinct advantages in replicating the pathophysiological traits of PD, while also functionally exploring potential treatment targets. In this review, we highlight the available gene- modified animal models related to various mechanisms of PD, including abnormal expression of alpha-synuclein protein, dysfunction of the autophagy-lysosome system, abnormalities in the ubiquitin-proteasome system, and mitochondrial dysfunction. We further discuss their respective strengths, limitations, and prospects, aiming to provide the most up to date information for the application of PD animal models and the advancement of anti-PD drugs.

Keywords: Autophagy-lysosome pathway; Gene editing; Mitochondrial dysfunction; Parkinson's disease; Ubiquitin-proteasome system; Α-Synuclein.

Publication types

  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified*
  • Autophagy / genetics
  • Disease Models, Animal*
  • Gene Editing* / methods
  • Humans
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • alpha-Synuclein / genetics

Substances

  • alpha-Synuclein