Format

Send to

Choose Destination
CNS Neurosci Ther. 2018 Mar;24(3):231-242. doi: 10.1111/cns.12802. Epub 2018 Jan 24.

Candesartan ameliorates brain inflammation associated with Alzheimer's disease.

Author information

1
Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beersheba, Israel.
2
Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beersheba, Israel.

Abstract

AIMS:

Alzheimer's disease (AD) pathology is associated with brain inflammation involving microglia and astrocytes. The renin-angiotensin system contributes to brain inflammation associated with AD pathology. This study aimed to investigate the role of candesartan, an angiotensin II type 1 receptor blocker, in modulation of glial functions associated with AD.

METHODS:

Focusing on the role of candesartan in glial inflammation, we evaluated inflammatory mediators' levels, secreted by lipopolysaccharide-induced microglia following candesartan treatment. Also, short-term intranasal candesartan effects on amyloid burden and microglial activation were investigated in 5 familial AD mice.

RESULTS:

Candesartan showed anti-inflammatory effects and shifted microglial activation toward a more neuroprotective phenotype. Candesartan decreased the lipopolysaccharide-induced nitric oxide synthase and cyclooxygenase-2 expression levels, which was accompanied by an induction of arginase-1 expression levels and enhanced Aβ1-42 uptake by microglia. Moreover, intranasally administered candesartan to AD mice model significantly reduced the amyloid burden and microglia activation in the hippocampus.

CONCLUSIONS:

These results thus shed light on the neuroprotective role of candesartan in the early stage of AD, which might relate to modulation of microglial activation states.

KEYWORDS:

Alzheimer's disease; angiotensin II; candesartan; glial inflammation

PMID:
29365370
PMCID:
PMC6489976
DOI:
10.1111/cns.12802
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center