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L-DOPA regulates neuroinflammation and Aβ pathology through NEP and ADAM17 in a mouse model of AD

Authors :
Hyun-ju Lee
JinHan Nam
Jeong-Woo Hwang
Jin-Hee Park
Yoo Joo Jeong
Ji-Yeong Jang
Su-Jeong Kim
A-Ran Jo
Hyang-Sook Hoe
Source :
Molecular Brain, Vol 17, Iss 1, Pp 1-5 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Dopamine plays important roles in cognitive function and inflammation and therefore is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Drugs that increase or maintain dopamine levels in the brain could be a therapeutic strategy for AD. However, the effects of dopamine and its precursor levodopa (L-DOPA) on Aβ/tau pathology in vivo and the underlying molecular mechanisms have not been studied in detail. Here, we investigated whether L-DOPA treatment alters neuroinflammation, Aβ pathology, and tau phosphorylation in 5xFAD mice, a model of AD. We found that L-DOPA administration significantly reduced microgliosis and astrogliosis in 5xFAD mice. In addition, L-DOPA treatment significantly decreased Aβ plaque number by upregulating NEP and ADAM17 levels in 5xFAD mice. However, L-DOPA-treated 5xFAD mice did not exhibit changes in tau hyperphosphorylation or tau kinase levels. These data suggest that L-DOPA alleviates neuroinflammatory responses and Aβ pathology but not tau pathology in this mouse model of AD.

Details

Language :
English
ISSN :
17566606
Volume :
17
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Molecular Brain
Publication Type :
Academic Journal
Accession number :
edsdoj.13e1166c72ae494aa46d707afb237d9c
Document Type :
article
Full Text :
https://doi.org/10.1186/s13041-024-01092-8