HASANTARI, Iris; NICOLAS, Nabil; ALZIEU, Philippe; LEVAL, Lea; SHALABI, Andree; GROLLEAU, Sylvain; DINET, Virginie

doi:10.3390/ijms25042272

HASANTARI, Iris
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

NICOLAS, Nabil
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

ALZIEU, Philippe
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

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Article de revue

Ce document a été publié dans

International Journal of Molecular Sciences. 2024-02-14, vol. 25, n° 4

Résumé en anglais

The complement is a component of the innate immune system designed to fight infections and tissue- or age-related damages. Complement activation creates an inflammatory microenvironment, which enhances cell death. Excessive complement inflammatory activity has been linked to alterations in the structure and functions of the blood-brain barrier, contributing to a poor prognosis for Alzheimer's disease (AD). In the AD preclinical phase, individuals are often clinically asymptomatic despite evidence of AD neuropathology coupled with heightened inflammation. Considering the involvement of the complement system in the risk of developing AD, we hypothesize that inhibiting complement activation could reduce this inflammatory period observed even before clinical signs, thereby slowing down the onset/progression of AD. To validate our hypothesis, we injected complement inhibitor factor H into the brain of APP/PS1 AD mice at early or late stages of this pathology. Our results showed that the injection of factor H had effects on both the onset and progression of AD by reducing proinflammatory IL6, TNF-α, IL1β, MAC and amyloid beta levels. This reduction was associated with an increase in VGLUT1 and Psd95 synaptic transmission in the hippocampal region, leading to an improvement in cognitive functions. This study invites a reconsideration of factor H's therapeutic potential for AD treatment.< Réduire

Mots clés en anglais

Mice

Animals

Alzheimer Disease

Amyloid beta-Peptides

Amyloid beta-Protein Precursor

Complement Factor H

Mice

Transgenic

Complement Activation

Disease Models

Animal

URI

https://oskar-bordeaux.fr/handle/20.500.12278/188968

DOI

http://dx.doi.org/10.3390/ijms25042272

Unités de recherche

Biologie des maladies cardiovasculaires (BMC) - UMR 1034

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Factor H's Control of Complement Activation Emerges as a Significant and Promising Therapeutic Target for Alzheimer's Disease Treatment.

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Résumé en anglais

Mots clés en anglais

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DOI

Unités de recherche