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

Alireza Minagar, Paul Shapshak, Robert Fujimura, Ray Ownby, Melvin Heyes, Carl Eisdorfer

Research output: Contribution to journalReview article

427 Scopus citations

Abstract

Macrophage/microglia (M∅) 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 effecter 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∅, 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∅ and astrocytes activation leading to neurotoxicity share similarities among the three diseases. Human Immunodeficiency Virus (HIV)-1-infected M∅ are involved in the pathogenesis of HAD and produce toxic molecules including cytokines, chemokines, and nitric oxide (NO). In AD, M∅s produce these molecules and are activated by β-amyloid proteins and related oligopeptides. Demyelination in MS involves M∅ that become lipid laden, spurred by several possible antigens. In these three diseases, cytokine/chemokine communications between M∅ and astrocytes occur and are involved in the balance of protective and destructive actions by these cells. This review describes the role of M∅ and astrocytes in the pathogenesis of these three progressive neurological diseases, examining both beneficent and deleterious effects in each disease.

Original languageEnglish (US)
Pages (from-to)13-23
Number of pages11
JournalJournal of the Neurological Sciences
Volume202
Issue number1-2
DOIs
StatePublished - Oct 15 2002

Keywords

  • Alzheimer disease
  • Astrocytes
  • HIV-associated dementia
  • Macrophage/microglia
  • Multiple sclerosis

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

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