Disruption of Endoplasmic Reticulum Proteostasis in Age-Related Nervous System Disorders.
Prog Mol Subcell Biol
; 59: 239-278, 2021.
Article
in En
| MEDLINE
| ID: mdl-34050870
ABSTRACT
Endoplasmic reticulum (ER) stress is a prominent cellular alteration of diseases impacting the nervous system that are associated to the accumulation of misfolded and aggregated protein species during aging. The unfolded protein response (UPR) is the main pathway mediating adaptation to ER stress, but it can also trigger deleterious cascades of inflammation and cell death leading to cell dysfunction and neurodegeneration. Genetic and pharmacological studies in experimental models shed light into molecular pathways possibly contributing to ER stress and the UPR activation in human neuropathies. Most of experimental models are, however, based on the overexpression of mutant proteins causing familial forms of these diseases or the administration of neurotoxins that induce pathology in young animals. Whether the mechanisms uncovered in these models are relevant for the etiology of the vast majority of age-related sporadic forms of neurodegenerative diseases is an open question. Here, we provide a systematic analysis of the current evidence linking ER stress to human pathology and the main mechanisms elucidated in experimental models. Furthermore, we highlight the recent association of metabolic syndrome to increased risk to undergo neurodegeneration, where ER stress arises as a common denominator in the pathogenic crosstalk between peripheral organs and the nervous system.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endoplasmic Reticulum
/
Proteostasis
Limits:
Animals
/
Humans
Language:
En
Journal:
Prog Mol Subcell Biol
Year:
2021
Document type:
Article
Affiliation country: