Cells in focus
Microglia: Proliferation and activation driven by the P2X7 receptor

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Abstract

Microglial activation is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD), Parkinsons’ disease, prion disease, multiple sclerosis, and ischemic and traumatic brain injury. The molecular mechanism of microglial activation is largely unknown. The expression of the purinergic, P2X7 receptor (P2X7R), is known to be enhanced in many brain pathologies where presence of activated microglia is a concurrent feature. This review focuses on the links between P2X7R expression and microglial activation and proliferation. The P2X7R is identified as a key player in the process of microgliosis, where by driving microglial activation, it can potentially lead to a deleterious cycle of neuroinflammation and neurodegeneration.

Section snippets

Cell origin and plasticity

The central nervous system (CNS) is composed of two major types of cells, neurons and glia. The name ‘glia’ is attributed to astrocytes and oligodendrocytes (both being of neuroectodermal origin), and microglia (‘brain macrophages’) of a monocytic lineage. Microglia are the immunoeffector cells of the CNS, participating in innate immune responses and communicating with other immunological cells via cytokines, chemokines and other bio-active substances. Microglia comprise approximately 10% of

Functions

The functions of microglia are not fully understood, but do include the following: (1) sensing and reacting to CNS injury, (2) removing cellular debris from the brain by phagocytosis, (3) regulating astrogliosis, (4) orchestrating neuroimmune function in CNS, and (5) assisting in the development of CNS (e.g., by secreting growth factors and removing apoptotic cells). Microglial functions can be modulatory, protective or deleterious to the functions of surrounding cells, including astrocytes and

Associated pathologies

Neuroinflammation signifies the brain's patterned response to insult with a number of immunomodulatory responses such as release of cytokines and chemokines set in motion with the activation of glia. Microglial-mediated neuroinflammation is associated with conditions such as AD, HIV-dementia, Parkinson's disease, prion disease, amyotrophic lateral sclerosis, and multiple sclerosis (Garden, 2002, Hall et al., 1998, McGeer et al., 1988, Tan et al., 1999). Chronic activation of microglia exposes

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