Genetic enhancement of macroautophagy in vertebrate models of neurodegenerative diseases

Patrick Ejlerskov, Avraham Ashkenazi, David C. Rubinsztein

Research output: Contribution to journalReview articlepeer-review

Abstract

Most of the neurodegenerative diseases that afflict humans manifest with the intraneuronal accumulation of toxic proteins that are aggregate-prone. Extensive data in cell and neuronal models support the concept that such proteins, like mutant huntingtin or alpha-synuclein, are substrates for macroautophagy (hereafter autophagy). Furthermore, autophagy-inducing compounds lower the levels of such proteins and ameliorate their toxicity in diverse animal models of neurodegenerative diseases. However, most of these compounds also have autophagy-independent effects and it is important to understand if similar benefits are seen with genetic strategies that upregulate autophagy, as this strengthens the validity of this strategy in such diseases. Here we review studies in vertebrate models using genetic manipulations of core autophagy genes and describe how these improve pathology and neurodegeneration, supporting the validity of autophagy upregulation as a target for certain neurodegenerative diseases.

Original languageAmerican English
Pages (from-to)3-8
Number of pages6
JournalNeurobiology of Disease
Volume122
DOIs
StatePublished - 1 Feb 2019
Externally publishedYes

Keywords

  • ATG5
  • ATG7
  • Autophagy
  • Beclin 1
  • Genetic therapy
  • Neurodegenerative disease

All Science Journal Classification (ASJC) codes

  • Neurology

Cite this