Failures in Protein Clearance Partly Underlie Late Onset Neurodegenerative Diseases and Link Pathology to Genetic Risk

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...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in neuroscience Vol. 13; p. 1304
Main Author Hardy, John
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 05.12.2019
Frontiers Media S.A
Subjects
Alzheimer’s disease
APP
Dementia
Disease
Gene expression
Gene loci
Genomics
Health risk assessment
Lipids
MAPT
Metabolism
Movement disorders
Mutation
Neurodegenerative diseases
Neuroscience
Parkinson's disease
Pathology
progressive supranuclear palsy
Proteasomes
Proteins
SNCA
Tau protein
Ubiquitin
United Kingdom > UK
APP
MAPT
Alzheimer’s disease
Parkinson’s disease
SNCA
progressive supranuclear palsy
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by: Illana Gozes, Tel Aviv University, Israel
Reviewed by: Anthony J. Turner, University of Leeds, United Kingdom; Elena Rybnikova, Pavlov Institute of Physiology (RAS), Russia
This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neuroscience
ISSN:1662-4548
1662-453X
1662-453X
DOI:10.3389/fnins.2019.01304