Adaptive immune regulation of glial homeostasis as an immunization strategy for neurodegenerative diseases

被引:30
作者
Kosloski, Lisa M. [1 ]
Ha, Duy M. [1 ]
Hutter, Jessica A. L. [1 ]
Stone, David K. [1 ]
Pichler, Michael R. [1 ]
Reynolds, Ashley D. [1 ]
Gendelman, Howard E. [1 ]
Mosley, R. Lee [1 ]
机构
[1] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA
基金
美国国家卫生研究院;
关键词
immunization; inflammation; microglia; neuroprotection; Parkinson's disease; regulatory T cells; therapeutic vaccination; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NITRATED ALPHA-SYNUCLEIN; NIGROSTRIATAL DOPAMINERGIC NEURODEGENERATION; EXPERIMENTAL AUTOIMMUNE-THYROIDITIS; PERIPHERAL BENZODIAZEPINE-RECEPTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; IMMUNOLOGICAL SELF-TOLERANCE; COLONY-STIMULATING FACTOR; CEREBRAL AMYLOID BURDEN; EARLY PARKINSON-DISEASE;
D O I
10.1111/j.1471-4159.2010.06834.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
P>Neurodegenerative diseases, notably Alzheimer's and Parkinson's diseases, are amongst the most devastating disorders afflicting the elderly. Currently, no curative treatments or treatments that interdict disease progression exist. Over the past decade, immunization strategies have been proposed to combat disease progression. Such strategies induce humoral immune responses against misfolded protein aggregates to facilitate their clearance. Robust adaptive immunity against misfolded proteins, however, accelerates disease progression, precipitated by induced effector T cell responses that lead to encephalitis and neuronal death. Since then, mechanisms that attenuate such adaptive neurotoxic immune responses have been sought. We propose that shifting the balance between effector and regulatory T cell activity can attenuate neurotoxic inflammatory events. This review summarizes advances in immune regulation to achieve a homeostatic glial response for therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are also discussed.
引用
收藏
页码:1261 / 1276
页数:16
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