Impact and Therapeutic Potential of PPARs in Alzheimer's Disease.

Neuroinflammation; PPAR; alzheimer`s disease; thiazolidinediones.; Pharmacology; Neurology; Neurology (clinical); Psychiatry and Mental Health; Pharmacology (medical); General Medicine

Abstract :

[en] Peroxisome proliferator activated receptors (PPARs) are well studied for their role of peripheral metabolism, but they also may be involved in the pathogenesis of various disorders of the central nervous system (CNS) including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's and, Parkinson's disease. The observation that PPARs are able to suppress the inflammatory response in peripheral macrophages and in several models of human autoimmune diseases, lead to the idea that PPARs might be beneficial for CNS disorders possessing an inflammatory component. The neuroinflammatory response during the course of Alzheimer's disease (AD) is triggered by the deposition of the β-amyloid peptide in extracellular plaques and ongoing neurodegeneration. Non-steroidal anti-inflammatory drugs (NSAIDs) have been considered to delay the onset and reduce the risk to develop Alzheimer's disease, while they also directly activate PPARγ. This led to the hypothesis that NSAID protection in AD may be partly mediated by PPARγ. Several lines of evidence have supported this hypothesis, using AD related transgenic cellular and animal models. Stimulation of PPARγ by synthetic agonist (thiazolidinediones) inducing anti-inflammatory, anti-amyloidogenic and insulin sensitizing effects may account for the observed effects. Several clinical trials already revealed promising results using PPARγ agonists, therefore PPARγ represents an attractive therapeutic target for the treatment of AD.

Disciplines :

Neurology

Author, co-author :

HENEKA, Michael ; University of Bonn, Department of Neurology, Clinical Neurosciences Unit, Bonn, Germany

Reyes-Irisarri, Elisabet; University of Bonn, Department of Neurology, Clinical Neurosciences Unit, Bonn, Germany

Hüll, Michael; University of Freiburg, Department of Psychiatry and Psychotherapy, Freiburg, Germany

Kummer, Markus P; University of Bonn, Department of Neurology, Clinical Neurosciences Unit, Bonn, Germany

External co-authors :

yes

Language :

English

Title :

Impact and Therapeutic Potential of PPARs in Alzheimer's Disease.

Publication date :

December 2011

Journal title :

Current Neuropharmacology

ISSN :

1570-159X

Publisher :

Bentham Science Publishers, United Arab Emirates

Volume :

Issue :

Pages :

643 - 650

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://eurekaselect.com/article/download/75881

Available on ORBilu :

since 07 May 2024

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