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LAMP2 deficiency attenuates the neurodegeneration markers induced by HSV-1 infection.
- Source :
-
Neurochemistry international [Neurochem Int] 2021 Jun; Vol. 146, pp. 105032. Date of Electronic Publication: 2021 Mar 27. - Publication Year :
- 2021
-
Abstract
- Mounting evidence suggests a major role of infectious agents in the pathogenesis of sporadic Alzheimer's disease (AD). Among them, herpes simplex virus type 1 (HSV-1) infection has emerged as a major factor in the etiology of AD. HSV-1 is able to induce some of the main alterations of the disease such as hyperphosphorylation of tau protein and accumulation of amyloid-β peptide. Functional genomic analysis of a cell model of HSV-1 infection and oxidative stress developed in our laboratory revealed lysosomal system to be the main pathway altered, and the lysosome-associated membrane protein 2 (LAMP2) gene one of the most strongly modulated genes. The aim of this work is to study LAMP2 as an AD candidate gene and to investigate its role in the neurodegeneration induced by HSV-1 using a LAMP2 knockdown cell model. LAMP2 deficiency led to a significant reduction of viral DNA replication and formation of infectious particles. In addition, tau hyperphosphorylation and inhibition of Aβ secretion induced by the virus were attenuated by the absence of LAMP2. Finally, genetic association studies revealed LAMP2 genetic variants to be associated with AD risk. In summary, our data indicate that LAMP2 could be a suitable candidate to mediate the AD-like phenotype caused by HSV-1.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Aged
Aged, 80 and over
Alzheimer Disease genetics
Alzheimer Disease virology
Animals
Cell Line, Tumor
Female
Gene Knockdown Techniques methods
Herpes Simplex genetics
Humans
Lysosomal-Associated Membrane Protein 2 antagonists & inhibitors
Lysosomal-Associated Membrane Protein 2 genetics
Male
Mice
Middle Aged
Neurodegenerative Diseases genetics
Neurodegenerative Diseases metabolism
Neurodegenerative Diseases virology
Alzheimer Disease metabolism
Herpes Simplex metabolism
Herpes Simplex prevention & control
Herpesvirus 1, Human metabolism
Lysosomal-Associated Membrane Protein 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9754
- Volume :
- 146
- Database :
- MEDLINE
- Journal :
- Neurochemistry international
- Publication Type :
- Academic Journal
- Accession number :
- 33781848
- Full Text :
- https://doi.org/10.1016/j.neuint.2021.105032