Modeling neuroinflammatory pathogenesis of Parkinson's disease.
The molecular mechanisms underlying the pathogenesis of idiopathic Parkinson's disease (PD) have not been completely elucidated; however, some progress has been made in identifying factors that compromise survival of the dopaminergic neurons in the substantia nigra (SN) the death of which give rise to the motor symptoms that enable clinicians to diagnose the disease in its mid- to late stages. The prevailing theory regarding processes that are likely to account for degeneration of the nigrostriatal system centers around mitochondrial dysfunction, oxidative stress, excitotoxicity, and neuroinflammation. Of these, neuroinflammation is one candidate that appears to accumulate more support with each passing year. A number of researchers have attempted to manipulate inflammation in various animal PD models with varying levels of success. Still others have used inflammatory stimuli to elicit nigral cell death (NCD), a disturbing finding that has prompted much interest. In this chapter, we attempt to integrate what is known about the role of neuroinflammation in PD with the factors we feel are critical for understanding how inflammation modulates disease progression.
Barnum
Christopher J
CJ
Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA.
Tansey
Malú G
MG
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D020267:MPTP Poisoning / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine; D010300:Parkinson Disease / Q000473:pathology* / Q000523:psychology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology; D010575:Pesticides / Q000633:toxicity; D013565:Sympatholytics
D008070:Lipopolysaccharides; D010575:Pesticides; D013565:Sympatholytics; D016627:Oxidopamine; D004298:Dopamine