Shining a light on autophagy in neurodegenerative diseases

Aswathy Chandran; Jean-Christophe Rochet

doi:10.1016/j.jbc.2021.101437

Shining a light on autophagy in neurodegenerative diseases

J Biol Chem. 2022 Jan;298(1):101437. doi: 10.1016/j.jbc.2021.101437. Epub 2021 Nov 19.

Authors

Aswathy Chandran¹, Jean-Christophe Rochet²

Affiliations

¹ Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, Indiana, USA. Electronic address: chandr49@purdue.edu.
² Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, Indiana, USA. Electronic address: jrochet@purdue.edu.

Abstract

Small-molecule modulators of autophagy have been widely investigated as potential therapies for neurodegenerative diseases. In a recent issue of JBC, Safren et al. described a novel assay that uses a photoconvertible fusion protein to identify compounds that alter autophagic flux. Autophagy inducers identified using this assay were found to either alleviate or exacerbate neurotoxicity in different cellular models of amyotrophic lateral sclerosis, challenging the notion that autophagy stimulation can be used as a one-size-fits-all therapy for neurodegenerative disease.

Keywords: Dendra2; LC3; amyotrophic lateral sclerosis; autophagic flux; autophagosome; autophagy; lysosome; neurodegenerative disease; protein aggregate; screening.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Comment

MeSH terms

Amyotrophic Lateral Sclerosis* / metabolism
Autophagy
Humans
Neurodegenerative Diseases* / metabolism

Grants and funding

R03 NS108229/NS/NINDS NIH HHS/United States