Neuroinflammation in Parkinson's disease: is there sufficient evidence for mechanism-based interventional therapy?
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.
Tansey
Malú G
MG
Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA. malu.tansey@utsouthwestern.edu
Frank-Cannon
Tamy C
TC
McCoy
Melissa K
MK
Lee
Jae Kyung
JK
Martinez
Terina N
TN
McAlpine
Fiona E
FE
Ruhn
Kelly A
KA
Tran
Thi A
TA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation; D008954:Models, Biological; D009410:Nerve Degeneration / Q000188:drug therapy; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000978:Antiparkinson Agents; D014409:Tumor Necrosis Factor-alpha