The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis.

Abstract

Macrophage/microglia (M phi) are the principal immune cells in the central nervous system (CNS) concomitant with inflammatory brain disease and play a significant role in the host defense against invading microorganisms. Astrocytes, as a significant component of the blood-brain barrier, behave as one of the immune effector cells in the CNS as well. However, both cell types may play a dual role, amplifying the effects of inflammation and mediating cellular damage as well as protecting the CNS. Interactions of the immune system, M phi, and astrocytes result in altered production of neurotoxins and neurotrophins by these cells. These effects alter the neuronal structure and function during pathogenesis of HIV-1-associated dementia (HAD), Alzheimer disease (AD), and multiple sclerosis (MS). HAD primarily involves subcortical gray matter, and both HAD and MS affect sub-cortical white matter. AD is a cortical disease. The process of M phi and astrocytes activation leading to neurotoxicity share similarities among the three diseases. Human Immunodeficiency Virus (HIV)-1-infected M phi are involved in the pathogenesis of HAD and produce toxic molecules including cytokines, chemokines, and nitric oxide (NO). In AD, M phis produce these molecules and are activated by beta-amyloid proteins and related oligopeptides. Demyelination in MS involves M phi that become lipid laden, spurred by several possible antigens. In these three diseases, cytokine/chemokine communications between M phi and astrocytes occur and are involved in the balance of protective and destructive actions by these cells. This review describes the role of M phi and astrocytes in the pathogenesis of these three progressive neurological diseases, examining both beneficent and deleterious effects in each disease.

0200400'04'06'08'10'12'14'16
Citations per Year

3,421 Citations

Semantic Scholar estimates that this publication has 3,421 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Minagar2002TheRO, title={The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis.}, author={Alireza Minagar and Paul Shapshak and Robert K Fujimura and Ray Ownby and Melvin Heyes and Carl Eisdorfer}, journal={Journal of the neurological sciences}, year={2002}, volume={202 1-2}, pages={13-23} }