Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases

Irena Kadiu, Jason G. Glanzer, Jonathan Kipnis, Howard Eliot Gendelman, Mark P. Thomas

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Brain mononuclear phagocytes (MP, bone marrow monocyte-derived macrophages, perivascular macrophages, and microglia) function to protect the nervous system by acting as debris scavengers, killers of microbial pathogens, and regulators of immune responses. MP are activated by a variety of environmental cues and such inflammatory responses elicit cell injury and death in the nervous system. MP immunoregulatory responses include secretion of neurotoxic factors, mobilization of adaptive immunity, and cell chemotaxis. This incites tissue remodelling and blood-brain barrier dysfunction. As disease progresses, MP secretions engage neighboring cells in a vicious cycle of autocrine and paracrine amplification of inflammation leading to tissue injury and ultimately destruction. Such pathogenic processes tilt the balance between the relative production of neurotrophic and neurotoxic factors, leading to disease progression. The ultimate effects that brain MP play in disease revolve "principally" around their roles in neurodegeneration. Importantly, common functions of brain MP in neuroimmunity link highly divergent diseases (for example, human immunodeficiency virus type-one associated dementia, Alzheimer's disease and Parkinson's disease). Research from our own laboratories and those of others seek to harness MP inflammatory processes with the intent of developing therapeutic interventions that block neurodegenerative processes and improve the quality of life in affected people.

Original languageEnglish (US)
Pages (from-to)25-50
Number of pages26
JournalNeurotoxicity Research
Volume8
Issue number1-2
DOIs
StatePublished - Dec 1 2005

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Neurodegenerative diseases
Phagocytes
Neurodegenerative Diseases
Macrophages
Nervous System
Brain
Nerve Growth Factors
Wounds and Injuries
Microglia
Neurology
Adaptive Immunity
Chemotaxis
Blood-Brain Barrier
Cues
Parkinson Disease
Dementia
Disease Progression
Alzheimer Disease
Cell Death
Quality of Life

Keywords

  • Alzheimer disease
  • HIV-1
  • HIV-1 associated dementia
  • Inflammation
  • Mononuclear Phagocytes
  • Neurodegeneration
  • Neuroimmunity
  • Neurotoxic factors
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases. / Kadiu, Irena; Glanzer, Jason G.; Kipnis, Jonathan; Gendelman, Howard Eliot; Thomas, Mark P.

In: Neurotoxicity Research, Vol. 8, No. 1-2, 01.12.2005, p. 25-50.

Research output: Contribution to journalArticle

Kadiu, Irena ; Glanzer, Jason G. ; Kipnis, Jonathan ; Gendelman, Howard Eliot ; Thomas, Mark P. / Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases. In: Neurotoxicity Research. 2005 ; Vol. 8, No. 1-2. pp. 25-50.
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