Autophagy in ageing and ageing-related neurodegenerative diseases

Cansu Karabiyik,So Jung Park,Rebecca A Frake,Mariana Pavel,David C Rubinsztein

doi:10.20517/and.2021.05

Abstract

Autophagy in ageing and ageing-related neurodegenerative diseases

Highlights

Autophagy is a term used to describe three pathways that deliver cytoplasmic contents to lysosomes for digestion and recycling
Rapamycin accelerated motor neuron degeneration and shortened lifespan in a transgenic mouse model of ALS expressing disease-causing mutant SOD-1, for instance[168]. This is suggested to relate to impaired autophagic flux in these animals, which is exacerbated by autophagy induction using rapamycin[168]
We can currently only speculate that autophagy induction would ameliorate age-related phenotypes in the brain and nervous system, neurodegeneration undeniably occurs predominantly against the backdrop of normal ageing

Summary

INTRODUCTION

Autophagy is a term used to describe three pathways that deliver cytoplasmic contents to lysosomes for digestion and recycling. Treatment with these two drugs increase the clearance of mutant tau and ameliorate the motor and morphological defects in an experimental zebrafish model expressing the human A152T disease-associated tau variant[52] Another class of compounds, the L-type Ca2+ channel antagonists (felodipine and verapamil) block the influx of extracellular Ca2+ and likely activate autophagy via the aforementioned Ca2+-AMPK axis. Rapamycin accelerated motor neuron degeneration and shortened lifespan in a transgenic mouse model of ALS expressing disease-causing mutant SOD-1 (human G93A SOD-1), for instance[168] This is suggested to relate to impaired autophagic flux in these animals, which is exacerbated by autophagy induction using rapamycin[168]. This result has been seen in Drosophila with rapamycin-induced lifespan extension dependent on expression of the core autophagy protein ATG5[207]

CONCLUSION

Findings

Availability of data and materials