Does neuroinflammation fan the flame in neurodegenerative diseases?

Tamy C. Frank-Cannon, Laura T. Alto, Fiona E. McAlpine, Mal G. Tansey

Research output: Contribution to journalArticle

404 Citations (Scopus)

Abstract

While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia) resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-perpetuating neuroinflammatory response that persists long after an initial injury or insult. Chronic neuroinflammation includes not only long-standing activation of microglia and subsequent sustained release of inflammatory mediators, but also the resulting increased oxidative and nitrosative stress. The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors. Neurodegenerative CNS disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), tauopathies, and age-related macular degeneration (ARMD), are associated with chronic neuroinflammation and elevated levels of several cytokines. Here we review the hallmarks of acute and chronic inflammatory responses in the CNS, the reasons why microglial activation represents a convergence point for diverse stimuli that may promote or compromise neuronal survival, and the epidemiologic, pharmacologic and genetic evidence implicating neuroinflammation in the pathophysiology of several neurodegenerative diseases.

Original languageEnglish (US)
Article number47
JournalMolecular Neurodegeneration
Volume4
Issue number1
DOIs
StatePublished - 2009

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Neurodegenerative Diseases
Microglia
Central Nervous System
Oxidative Stress
Tauopathies
Cytokines
Central Nervous System Diseases
Huntington Disease
Wounds and Injuries
Amyotrophic Lateral Sclerosis
Macular Degeneration
Chemokines
Multiple Sclerosis
Parkinson Disease
Immune System
Alzheimer Disease
Stroke
Phenotype
Infection

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Clinical Neurology
  • Molecular Biology

Cite this

Frank-Cannon, T. C., Alto, L. T., McAlpine, F. E., & Tansey, M. G. (2009). Does neuroinflammation fan the flame in neurodegenerative diseases? Molecular Neurodegeneration, 4(1), [47]. https://doi.org/10.1186/1750-1326-4-47

Does neuroinflammation fan the flame in neurodegenerative diseases? / Frank-Cannon, Tamy C.; Alto, Laura T.; McAlpine, Fiona E.; Tansey, Mal G.

In: Molecular Neurodegeneration, Vol. 4, No. 1, 47, 2009.

Research output: Contribution to journalArticle

Frank-Cannon, Tamy C. ; Alto, Laura T. ; McAlpine, Fiona E. ; Tansey, Mal G. / Does neuroinflammation fan the flame in neurodegenerative diseases?. In: Molecular Neurodegeneration. 2009 ; Vol. 4, No. 1.
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