Ubiquitin signaling in neurodegenerative diseases: an autophagy and proteasome perspective.

Cell Death and Differentiation
François Le Guerroué, Richard J Youle

Abstract

Ubiquitin signaling is a sequence of events driving the fate of a protein based on the type of ubiquitin modifications attached. In the case of neurodegenerative diseases, ubiquitin signaling is mainly associated with degradation signals to process aberrant proteins, which form aggregates often fatal for the brain cells. This signaling is often perturbed by the aggregates themselves and leads to the accumulation of toxic aggregates and inclusion bodies that are deleterious due to a toxic gain of function. Decrease in quality control pathways is often seen with age and is a critical onset for the development of neurodegeneration. Many aggregates are now thought to propagate in a prion-like manner, where mutated proteins acting like seeds are transitioning from cell to cell, converting normal proteins to toxic aggregates. Modulation of ubiquitin signaling, by stimulating ubiquitin ligase activation, is a potential therapeutic strategy to treat patients with neurodegeneration diseases.

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Citations

Jan 9, 2021·Cell Death and Differentiation·Marlene F SchmidtGrant Dewson
Feb 8, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·April L Darling, James Shorter
Jan 16, 2021·Cell Death and Differentiation·Rune Busk Damgaard
Apr 4, 2021·International Journal of Molecular Sciences·Paula SanchoSergio Aguilera-Albesa
May 24, 2021·Ageing Research Reviews·Hyeon-Ah Do, Kwang-Hyun Baek
Jul 13, 2021·Frontiers in Aging Neuroscience·Dunja PetrovicMilos R Filipovic

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Methods Mentioned

BETA
ubiquitination
protein folding
two hybrid
transfection

Software Mentioned

AUTAC
AUTACs
PROTAC

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