DOCK2 is a microglial specific regulator of central nervous system innate immunity found in normal and Alzheimer's disease brain

Patrick J. Cimino, Izabela Sokal, James Leverenz, Yoshinori Fukui, Thomas J. Montine

研究成果: Contribution to journalArticle査読

28 被引用数 (Scopus)

抄録

Neuroinflammation is a hallmark of several neurodegenerative diseases, including Alzheimer's disease (AD). Strong epidemiological and experimental evidence supports the use of nonsteroidal anti-inflammatory drugs to reduce AD risk. However, poor outcome in clinical trials and toxicity in a prevention trial have shifted focus away from these cyclooxygenase (COX) inhibitors to seek additional therapeutic targets in the prostaglandin pathway. Previously, the prostaglandin E2 receptor, EP2, was shown to regulate neuroinflammation and reduce Aβ plaque burden in transgenic mice. Unfortunately, widespread EP2 distribution and a direct effect on COX2 induction make EP2 a less desirable target. In this study, we link dedicator of cytokinesis 2 (DOCK2) to the prostaglandin pathway in the brain. Additionally, we show that DOCK2 regulates microglial innate immunity independent of COX2 induction and that DOCK2 + microglia are associated with human AD pathology. Together, these results suggest DOCK2 as a COX2 expression-independent therapeutic target for neurodegenerative diseases such as AD.

本文言語英語
ページ(範囲)1622-1630
ページ数9
ジャーナルAmerican Journal of Pathology
175
4
DOI
出版ステータス出版済み - 2009

All Science Journal Classification (ASJC) codes

  • 病理学および法医学

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