TY - JOUR
T1 - Neuroinflammation, oxidative stress, and the pathogenesis of Parkinson's disease
AU - Lee Mosley, R.
AU - Benner, Eric J.
AU - Kadiu, Irena
AU - Thomas, Mark
AU - Boska, Michael D.
AU - Hasan, Khader
AU - Laurie, Chad
AU - Gendelman, Howard E.
N1 - Funding Information:
The authors thank Ms. Robin Taylor for excellent graphic and administrative assistance. The National Institutes of Health (NIH) grants that supported this work included R21 NS049264 (to R.L.M.) and P01 NS31492, R01 NS34239, P01 NS043985, and R37 NS36136 and P01 MH64570-03 (to H.E.G.).
PY - 2006/12
Y1 - 2006/12
N2 - Neuroinflammatory processes play a significant role in the pathogenesis of Parkinson's disease (PD). Epidemiologic, animal, human, and therapeutic studies all support the presence of a neuroinflammatory cascade in disease. This is highlighted by the neurotoxic potential of microglia. In steady-state, microglia serve to protect the nervous system by acting as debris scavengers, killers of microbial pathogens, and regulators of innate and adaptive immune responses. In neurodegenerative diseases, activated microglia affect neuronal injury and death through production of glutamate, pro-inflammatory factors, reactive oxygen species, quinolinic acid among others and by mobilization of adaptive immune responses and cell chemotaxis leading to transendothelial migration of immunocytes across the blood-brain barrier and perpetuation of neural damage. As disease progresses, inflammatory secretions engage neighboring glial cells, including astrocytes and endothelial cells, resulting in a vicious cycle of autocrine and paracrine amplification of inflammation perpetuating tissue injury. Such pathogenic processes contribute to neurodegeneration in PD. Research from others and our own laboratories seek to harness such inflammatory processes with the singular goal of developing therapeutic interventions that positively affect the tempo and progression of human disease.
AB - Neuroinflammatory processes play a significant role in the pathogenesis of Parkinson's disease (PD). Epidemiologic, animal, human, and therapeutic studies all support the presence of a neuroinflammatory cascade in disease. This is highlighted by the neurotoxic potential of microglia. In steady-state, microglia serve to protect the nervous system by acting as debris scavengers, killers of microbial pathogens, and regulators of innate and adaptive immune responses. In neurodegenerative diseases, activated microglia affect neuronal injury and death through production of glutamate, pro-inflammatory factors, reactive oxygen species, quinolinic acid among others and by mobilization of adaptive immune responses and cell chemotaxis leading to transendothelial migration of immunocytes across the blood-brain barrier and perpetuation of neural damage. As disease progresses, inflammatory secretions engage neighboring glial cells, including astrocytes and endothelial cells, resulting in a vicious cycle of autocrine and paracrine amplification of inflammation perpetuating tissue injury. Such pathogenic processes contribute to neurodegeneration in PD. Research from others and our own laboratories seek to harness such inflammatory processes with the singular goal of developing therapeutic interventions that positively affect the tempo and progression of human disease.
KW - Diffusion tensor imaging (DTI)
KW - Dopaminergic neurodegeneration
KW - Dopaminergic neurons
KW - Free radicals
KW - Inflammation
KW - Microglia
KW - Oxidative stress
KW - Parkinson's disease
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U2 - 10.1016/j.cnr.2006.09.006
DO - 10.1016/j.cnr.2006.09.006
M3 - Article
C2 - 18060039
AN - SCOPUS:33845211714
SN - 1566-2772
VL - 6
SP - 261
EP - 281
JO - Clinical Neuroscience Research
JF - Clinical Neuroscience Research
IS - 5
ER -