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Modulation of Microglial Innate Immunity in Alzheimer's Disease by Activation of Peroxisome Proliferator-activated Receptor Gamma

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Abstract:

Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Although the etiology of AD remains unclear, microglia-mediated neuroinflammation is believed to play an important role in its pathogenesis. Microglial activation occurs in AD and is characterized by apparent phagocytic activity and by increased production and secretion of several cytokines, chemokines, reactive oxygen and nitrogen species, prostaglandin (PG)E2, and neurotrophic factors. Microglial activation can be neuroprotective through the release of neurotrophic factors and by phagocytosing Aβ, a critical neurotoxic component in AD brain. Concurrently, microglial activation causes elevated inflammatory responses that lead to paracrine damage to neurons. Therefore, a well-controlled microglial activation that diminishes microglial-mediated oxidative damage while promoting neuronal protection may be the key for AD therapy. Peroxisome proliferator-activated receptor gamma (PPARγ) has recently gained increasing attention in AD due to its function as a molecular target for nonsteroidal anti-inflammatory drugs (NSAIDs). In this review, we will discuss the role of PPARγ in microglial innate immunity in AD and how pharmacological manipulation of microglial activation using PPARγ ligands might facilitate the treatment of AD.

Keywords: Alzheimer's disease; PPARγ; microglial activation; neuroinflammation; therapy; β-amyloid

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709787458399

Affiliations: Division of Mental Health and Substance Abuse Research, National Health Research Institutes, No.35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, R.O.C.

Publication date: February 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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