Authors: De Simone, Roberta¹; Ajmone-Cat, Maria¹; Minghetti, Luisa²

Source: Molecular Neurobiology, Volume 29, Number 2, April 2004 , pp. 197-212(16)

Publisher: Humana Press

Abstract:

In the central nervous system (CNS), apoptosis plays an important role during development and is a primary pathogenic mechanism in several adult neurodegenerative diseases. A main feature of apoptotic cell death is the efficient and fast removal of dying cells by macrophages and nonprofessional phagocytes, without eliciting inflammation in the surrounding tissue. Apoptotic cells undergo several membrane changes, including the externalization of so-called “eat me” signals whose cognate receptors are present on professional phagocytes. Among these signals, the aminophospholipid phosphatidylserine (PS) appears to have a crucial and unique role in preventing the classical pro-inflammatory activation of macrophages, thus ensuring the silent and safe removal of apoptotic cells. Although extensively studied in the peripheral organs, the process of recognition and removal of apoptotic cells in the brain has only recently begun to be unraveled. Here, we summarize the evidence suggesting that upon interaction with PS-expressing apoptotic neurons, microglia may no longer promote the inflammatory cascade, but rather facilitate the elimination of damaged neurons through antiinflammatory and neuroprotective functions. We propose that the anti-inflammatory microglial phenotype induced through the activation of the specific PS receptor (PtdSerR), expressed by resting and activated microglial cells, could be relevant to the final outcome of neurodegenerative diseases, in which apoptosis seems to play a crucial role.

Keywords: Apoptosis; brain macrophages; cytokine; inflammation; nerve growth factor; neurodegeneration; nitric oxide; microglial activation; prostaglandin E2; transforming growth factor-β

Document Type: Research article

DOI: http://dx.doi.org/10.1385/MN:29:2:197

Affiliations: 1: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Italy, 2: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Italy, Email: luisa.minghetti@iss.it

Publication date: 2004-04-01

Related content

• In this: publication
• By this: publisher
• In this Subject: Anatomy & Physiology ,  Zoology
• By this author: De Simone, Roberta ;  Ajmone-Cat, Maria ;  Minghetti, Luisa

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers