Neurotoxicity Research

, Volume 8, Issue 1, pp 25–50

Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases

  • Irena Kadiu
  • Jason G. Glanzer
  • Jonathan Kipnis
  • Howard E. Gendelman
  • Mark P. Thomas
Part I HIV-1 Asociated Dementia (HAD)

DOI: 10.1007/BF03033818

Cite this article as:
Kadiu, I., Glanzer, J.G., Kipnis, J. et al. neurotox res (2005) 8: 25. doi:10.1007/BF03033818

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.

Keywords

Mononuclear PhagocytesNeurodegenerationAlzheimer diseaseInflammationNeuroimmunityHIV-1HIV-1 associated dementiaParkinson’s diseaseNeurotoxic factors

Copyright information

© Springer 2005

Authors and Affiliations

  • Irena Kadiu
    • 1
  • Jason G. Glanzer
    • 1
  • Jonathan Kipnis
    • 1
  • Howard E. Gendelman
    • 1
  • Mark P. Thomas
    • 1
  1. 1.Laboratory of Neuroregeneration, Department of Pharmacology and Experimental Neuroscience, Center for Neurovirology and Neurodegenerative DisordersUniversity of Nebraska Medical CenterOmaha