SUMOylation, aging and autophagy in neurodegeneration

Shamini Vijayakumaran; Dean L Pountney

doi:10.1016/j.neuro.2018.02.015

SUMOylation, aging and autophagy in neurodegeneration

Neurotoxicology. 2018 May:66:53-57. doi: 10.1016/j.neuro.2018.02.015. Epub 2018 Mar 2.

Authors

Shamini Vijayakumaran¹, Dean L Pountney²

Affiliations

¹ Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia.
² Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia. Electronic address: d.pountney@griffith.edu.au.

PMID: 29490232
DOI: 10.1016/j.neuro.2018.02.015

Abstract

Protein homeostasis is essential for the wellbeing of several cellular systems. Post-translational modifications (PTM) coordinate various pathways in response to abnormal aggregation of proteins in neurodegenerative disease states. In the presence of accumulating misfolded proteins and toxic aggregates, the small ubiquitin-like modifier (SUMO) is associated with various substrates, including chaperones and other recruited factors, for refolding and for clearance via proteolytic systems, such as the ubiquitin-proteasome pathway (UPS), chaperone-mediated autophagy (CMA) and macroautophagy. However, these pathological aggregates are also known to inhibit both the UPS and CMA, further creating a toxic burden on cells. This review suggests that re-routing cytotoxic aggregates towards selective macroautophagy by modulating the SUMO pathway could provide new mechanisms towards neuroprotection.

Keywords: Autophagy; Misfolded protein; N; Post-translational modifications; Small-Ubiquitin-like modifier.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Aging*
Animals
Autophagy*
Humans
Molecular Chaperones / metabolism
Neurodegenerative Diseases / metabolism*
Neuroprotection
Sumoylation*

Substances

Molecular Chaperones