Hardy, J;
(2019)
Failures in Protein Clearance Partly Underlie Late Onset Neurodegenerative Diseases and Link Pathology to Genetic Risk.
Frontiers in Neuroscience
, 13
, Article 1304. 10.3389/fnins.2019.01304.
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Abstract
As we identify the loci involved in late onset neurodegenerative disease, we are finding that the majority of them are involved in damage response processes. In this short review, I propose that it is partly a failure in these damage response processes which underlie late onset disease and that the resultant pathology is a marker of the type of damage response which has failed: microglial clearance of damaged neuronal membranes in Alzheimer’s disease (AD), ubiquitin proteasome clearance in the tauopathies, and lysosomal clearance in Parkinson’s disease (PD). In this review, I outline this relationship. This article is not intended as a comprehensive review of the cell biology of any of these disorders but rather a summary of the evidence that the genetics and pathology of these disorders appear to point, in each case, to the removal of misfolded proteins as a critical process in disease pathogenesis.
| Type: | Article |
|---|---|
| Title: | Failures in Protein Clearance Partly Underlie Late Onset Neurodegenerative Diseases and Link Pathology to Genetic Risk |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnins.2019.01304 |
| Publisher version: | https://doi.org/10.3389/fnins.2019.01304 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, APP, MAPT, SNCA, ALZHEIMERS-DISEASE, ALPHA-SYNUCLEIN, AMYLOID HYPOTHESIS, TAU, ASSOCIATION, MUTATIONS, HAPLOTYPE, VARIANTS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10091636 |
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