학술논문
Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing
Document Type
Report
Author
Boland, Barry; Yu, Wai Haung; Corti, Olga; Mollereau, Bertrand; Henriques, Alexandre; Bezard, Erwan; Pastores, Greg M.; Rubinsztein, David C.; Nixon, Ralph A.; Duchen, Michael R.; Mallucci, Giovanna R.; Kroemer, Guido; Levine, Beth; Eskelinen, Eeva-Liisa; Mochel, Fanny; Spedding, Michael; Louis, Caroline; Martin, Olivier R.; Millan, Mark J.
Source
Nature Reviews Drug Discovery. September 2018, Vol. 17 Issue 9, p660, 29 p.
Subject
Language
English
ISSN
1474-1776
Abstract
Author(s): Barry Boland [1, 27]; Wai Haung Yu [2, 27]; Olga Corti [3]; Bertrand Mollereau [4]; Alexandre Henriques [5]; Erwan Bezard [6]; Greg M. Pastores [7]; David C. Rubinsztein [8]; [...]
Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and amyotrophic lateral sclerosis represent a major socio-economic challenge in view of their high prevalence yet poor treatment. They are often called 'proteinopathies' owing to the presence of misfolded and aggregated proteins that lose their physiological roles and acquire neurotoxic properties. One reason underlying the accumulation and spread of oligomeric forms of neurotoxic proteins is insufficient clearance by the autophagic-lysosomal network. Several other clearance pathways are also compromised in NDAs: chaperone-mediated autophagy, the ubiquitin-proteasome system, extracellular clearance by proteases and extrusion into the circulation via the blood-brain barrier and glymphatic system. This article focuses on emerging mechanisms for promoting the clearance of neurotoxic proteins, a strategy that may curtail the onset and slow the progression of NDAs.
Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and amyotrophic lateral sclerosis represent a major socio-economic challenge in view of their high prevalence yet poor treatment. They are often called 'proteinopathies' owing to the presence of misfolded and aggregated proteins that lose their physiological roles and acquire neurotoxic properties. One reason underlying the accumulation and spread of oligomeric forms of neurotoxic proteins is insufficient clearance by the autophagic-lysosomal network. Several other clearance pathways are also compromised in NDAs: chaperone-mediated autophagy, the ubiquitin-proteasome system, extracellular clearance by proteases and extrusion into the circulation via the blood-brain barrier and glymphatic system. This article focuses on emerging mechanisms for promoting the clearance of neurotoxic proteins, a strategy that may curtail the onset and slow the progression of NDAs.