Neuroinflammation in Parkinson's disease: is there sufficient evidence for mechanism-based interventional therapy?

Abstract

The inflammatory response in the brain associated with most chronic neurodegenerative diseases is termed neuroinflammation. Neuropathological and neuroradiological studies indicate that in certain neurodegenerative disorders neuroinflammation may be detectable years before significant loss of neurons occurs. In this review, we discuss the evidence from human studies and experimental models that implicate neuroinflammatory processes in the progressive neurodegeneration of the nigrostriatal pathway, the hallmark of Parkinson's Disease (PD). We discuss the neurotoxic role of microglia-derived inflammatory mediators which are suspected to hasten the death of nigral dopaminergic neurons, in particular the pro-inflammatory cytokine Tumor Necrosis Factor (TNF) and its downstream signaling pathways. We also entertain the possibility that chronic microglia activation links proteinopathies to neurodegeneration. The rationale for current and future use of anti-inflammatory approaches to protect vulnerable neuronal populations in PD is also reviewed.

• Authors: Malú G Tansey, Tamy C Frank-Cannon, Melissa K McCoy, Jae Kyung Lee, Terina N Martinez, Fiona E McAlpine, Kelly A Ruhn, Thi A Tran
• Journal: Frontiers in bioscience : a journal and virtual library (Front Biosci) Vol. 13 Pg. 709-17 (Jan 01 2008) ISSN: 1093-9946 [Print] United States
• PMID: 17981581 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Inflammatory Agents
• Antiparkinson Agents
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antiparkinson Agents (therapeutic use)
• Brain (pathology)
• Disease Models, Animal
• Humans
• Inflammation
• Models, Biological
• Nerve Degeneration (drug therapy)
• Neurons (metabolism)
• Oxidative Stress
• Parkinson Disease (epidemiology, immunology, therapy)
• Tumor Necrosis Factor-alpha (metabolism)