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CNS Drugs

, Volume 22, Issue 1, pp 1–14 | Cite as

The Role of Peroxisome Proliferator-Activated Receptor-γ PPARγ) in Alzheimer’s Disease

Therapeutic Implications
  • Qingguang Jiang
  • Michael Heneka
  • Gary E. Landreth
Leading Article

Abstract

Alzheimer’s disease is a complex neurodegenerative disorder, with aging, genetic and environmental factors contributing to its development and progression. The complexity of Alzheimer’s disease presents substantial challenges for the development of new therapeutic agents. Alzheimer’s disease is typified by pathological depositions of β-amyloid peptides and neurofibrillary tangles within the diseased brain. It has also been demonstrated to be associated with a significant microglia-mediated inflammatory component, dysregulated lipid homeostasis and regional deficits in glucose metabolism within the brain. The peroxisome proliferator-activated receptor-γ (PPARγ) is a prototypical ligand-activated nuclear receptor that coordinates lipid, glucose and energy metabolism, and is found in elevated levels in the brains of individuals with Alzheimer’s disease. A recently appreciated physiological function of this type of receptor is its ability to modulate inflammatory responses. In animal models of Alzheimer’s disease, PPARγ agonist treatment results in the reduction of amyloid plaque burden, reduced inflammation and reversal of disease-related behavioural impairment. In a recent phase II clinical trial, the use of the PPARγ agonist rosiglitazone was associated with improved cognition and memory in patients with mild to moderate Alzheimer’s disease. Thus, PPARγ may act to modulate multiple pathophysiological mechanisms that contribute to Alzheimer’s disease, and represents an attractive therapeutic target for the treatment of the disease.

Keywords

Insulin Resistance Ibuprofen Rosiglitazone Pioglitazone Tg2576 Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by grants from the NIH (AG16704 and AG030482) and the Blanchette Hooker Rockefeller Foundation. Michael Heneka was supported by grants from the Deutsche Forschungsgemeinschaft and gave an oral presentation at the 2007 Solvay Pharmaceuticals Scientific Symposium on PPARγ in Alzheimer’s disease. Case Western Reserve University holds a US patent on the use of PPARγ agonists in Alzheimer’s disease and other CNS indications with an inflammatory component. Qingguang Jiang has no conflicts of interest that are directly relevant to the content of this review.

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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Qingguang Jiang
    • 1
  • Michael Heneka
    • 2
  • Gary E. Landreth
    • 1
  1. 1.Department of Neurosciences, Alzheimer Research LaboratorySchool of Medicine, Case Western Reserve UniversityClevelandUSA
  2. 2.Department of Neurology, Molecular Neurobiology UnitUniversity of MunsterMunsterGermany

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