Achucarro Seminars

17 Feb [2017]

at 13.00 CET

Inflammation as therapeutic target for Alzheimer's disease

Magdalena Sastre

Imperial College London (UK)


Abstract

Alzheimer's disease (AD) amyloid-β (Aβ) deposition is associated with a local inflammatory response in the brain, promoting the progression of neurodegeneration. Clusters of activated microglia surrounding the amyloid plaques have been detected in post-mortem examination of brains of AD patients and in animal models. However, the exact role of neuroinflammation in AD still remains unclear, because depending on their phenotype they could have protective vs neurotoxic effects. Glial cells can release neurotoxic molecules such as pro-inflammatory cytokines and other immune mediators such as reactive oxygen species, which are also able to increases the levels of BACE1, the main enzyme implicated in the generation of Aβ, therefore creating a vicious cycle. Interestingly, consensus binding sites for various transcription factors that are known to be regulated by inflammation (such as NFκB, PPARγ and STAT1) are present in the BACE1 promoter. PPARγ activity is regulated by cofactors such as the PPARγ coactivator-1α (PGC-1α), which is a transcriptional regulator that controls major metabolic functions through the co-activation of PPARγ and other transcription factors. During this talk I will present 1) results of in vivo imaging of microglia using positron emission tomography in the 5XFAD model of AD; 2) our recent data of PGC-1α gene delivery using viral vectors in a model of amyloidosis at pre-symptomatic stages of AD.

 

http://www.imperial.ac.uk/people/m.sastre

 

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