Neuroinflammation, oxidative stress, and the pathogenesis of Parkinson's disease

被引:275
作者
Mosley, R. Lee
Benner, Eric J.
Kadiu, Irena
Thomas, Mark
Boska, Michael D.
Hasan, Khader
Laurie, Chad
Gendelman, Howard E.
机构
[1] Univ Nebraska, Med Ctr, Dept Pharmacol & Expt Neurosci, Ctr Neurovirol & Neurodegenerat Disorders, Omaha, NE 68198 USA
[2] Univ Nebraska, Med Ctr, Dept Radiol, Omaha, NE 68105 USA
[3] Univ Texas, Sch Med, Dept Diagnost & Intervent Imaging, Houston, TX USA
关键词
Parkinson's disease; inflammation; oxidative stress; microglia; dopaminergic neurons; diffusion tensor imaging (DTI); free radicals; dopaminergic neurodegeneration;
D O I
10.1016/j.cnr.2006.09.006
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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. (C) 2006 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:261 / 281
页数:21
相关论文
共 271 条
[1]   GLUTATHIONE LEVELS IN SPECIFIC BRAIN-REGIONS OF GENETICALLY EPILEPTIC (TG/TG) MICE [J].
ABBOTT, LC ;
NEJAD, HH ;
BOTTJE, WG ;
HASSAN, AS .
BRAIN RESEARCH BULLETIN, 1990, 25 (04) :629-631
[2]   Alteration of 8-hydroxyguanosine concentrations in the cerebrospinal fluid and serum from patients with Parkinson's disease [J].
Abe, T ;
Isobe, C ;
Murata, T ;
Sato, C ;
Tohgi, H .
NEUROSCIENCE LETTERS, 2003, 336 (02) :105-108
[3]   MICROGLIAL RESPONSE TO 6-HYDROXYDOPAMINE-INDUCED SUBSTANTIA NIGRA LESIONS [J].
AKIYAMA, H ;
MCGEER, PL .
BRAIN RESEARCH, 1989, 489 (02) :247-253
[4]  
Alam ZI, 1997, J NEUROCHEM, V69, P1326
[5]   Oxidative DNA damage in the parkinsonian brain: An apparent selective increase in 8-hydroxyguanine levels in substantia nigra [J].
Alam, ZI ;
Jenner, A ;
Daniel, SE ;
Lees, AJ ;
Cairns, N ;
Marsden, CD ;
Jenner, P ;
Halliwell, B .
JOURNAL OF NEUROCHEMISTRY, 1997, 69 (03) :1196-1203
[6]   Intracerebral regulation of immune responses [J].
Aloisi, F ;
Ambrosini, E ;
Columba-Cabezas, S ;
Magliozzi, R ;
Serafini, B .
ANNALS OF MEDICINE, 2001, 33 (08) :510-515
[7]   Oxidative stress in neurodegeneration: cause or consequence? [J].
Andersen, JK .
NATURE MEDICINE, 2004, 10 (07) :S18-S25
[8]   Therapeutic vaccine for acute and chronic motor neuron diseases: Implications for amyotrophic lateral sclerosis [J].
Angelov, DN ;
Waibel, S ;
Guntinas-Lichius, O ;
Lenzen, M ;
Neiss, WF ;
Tomov, TL ;
Yoles, E ;
Kipnis, J ;
Schori, H ;
Reuter, A ;
Ludolph, A ;
Schwartz, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (08) :4790-4795
[9]  
Aoyama K, 2000, ANN NEUROL, V47, P524, DOI 10.1002/1531-8249(200004)47:4<524::AID-ANA19>3.0.CO
[10]  
2-5