Molecular Neurobiology

, Volume 29, Issue 2, pp 197–212 | Cite as

Atypical antiinflammatory activation of microglia induced by apoptotic neurons

Possible role of phosphatidylserine-phosphatidylserine receptor interaction
  • Roberta De Simone
  • Maria Antonietta Ajmone-Cat
  • Luisa Minghetti


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.

Index Entries

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


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Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Roberta De Simone
    • 1
  • Maria Antonietta Ajmone-Cat
    • 1
  • Luisa Minghetti
    • 1
  1. 1.Department of Cell Biology and NeurosciencesIstituto Superiore di SanitàItaly

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