%0 Journal Article
%T Sweepers in the CNS: Microglial Migration and Phagocytosis in the Alzheimer Disease Pathogenesis
%A Mariko Noda
%A Akio Suzumura
%J International Journal of Alzheimer's Disease
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/891087
%X Microglia are multifunctional immune cells in the central nervous system (CNS). In the neurodegenerative diseases such as Alzheimer's disease (AD), accumulation of glial cells, gliosis, occurs in the lesions. The role of accumulated microglia in the pathophysiology of AD is still controversial. When neuronal damage occurs, microglia exert diversified functions, including migration, phagocytosis, and production of various cytokines and chemokines. Among these, microglial phagocytosis of unwanted neuronal debris is critical to maintain the healthy neuronal networks. Microglia express many surface receptors implicated in phagocytosis. It has been suggested that the lack of microglial phagocytosis worsens pathology of AD and induces memory impairment. The present paper summarizes recent evidences on implication of microglial chemotaxis and phagocytosis in AD pathology and discusses the mechanisms related to chemotaxis toward injured neurons and phagocytosis of unnecessary debris. 1. Introduction Microglia are macrophage-like resident immune cells in the central nervous system (CNS) and possess both neurotoxic and neuroprotective function. Microglia accumulate in the lesions of a variety of neurodegenerative disorders, such as Alzheimer¡¯s disease (AD), Parkinson¡¯s disease, and multiple sclerosis, and are thought to play both toxic and protective functions for neuronal survival [1]. Microglia are considered to be a first line defense and respond quickly to various stimuli. When activated, microglia undergo morphological changes to ameboid, proliferate, migrate toward injured areas, and release many soluble factors and phagocytosis of foreign substances or unwanted self-debris. Appropriate migration of microglia to damaged area is controlled by chemokines and nucleotide ATP [2, 3]. Phagocytosis seems to be important to prevent the senile plaque expansion in AD by removing amyloid ¦Â (A¦Â) deposit [4]. Microglia not only engulf the A¦Â protein but also phagocytose apoptotic cells and degenerated neuronal debris. Phagocytosis of apoptotic or degenerated neuronal debris is crucial to reduce inflammation and maintain healthy neuronal networks. Another type of phagocytosis, phagocytosis with inflammation, occurs in chronic inflammatory-related neurodegenerative disorders including Alzheimer disease [5¨C7]. Degenerated neurons releases several signaling molecules, including nucleotides, cytokines, and chemokines, to recruit microglia and enhance their activities [8, 9]. The phenomenon are now termed as find-me, eat-me, and help-me signals. In this paper, we focused on
%U http://www.hindawi.com/journals/ijad/2012/891087/