Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA.
J Neurochem. 2010 Sep 1;114(5):1261-76. doi: 10.1111/j.1471-4159.2010.06834.x. Epub 2010 May 26.
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.
神经退行性疾病,特别是阿尔茨海默病和帕金森病,是困扰老年人的最具破坏性的疾病之一。目前,尚无治愈或阻止疾病进展的治疗方法。在过去的十年中,已经提出了免疫策略来对抗疾病进展。这些策略诱导针对错误折叠蛋白聚集体的体液免疫反应,以促进其清除。然而,针对错误折叠蛋白的强大适应性免疫会加速疾病进展,这是由诱导的效应 T 细胞反应引起的,导致脑炎和神经元死亡。从那时起,人们一直在寻找减轻这种适应性神经毒性免疫反应的机制。我们提出,改变效应 T 细胞和调节性 T 细胞活性之间的平衡可以减轻神经毒性炎症事件。本综述总结了免疫调节方面的进展,以实现针对治疗获益的神经胶质反应的平衡。还讨论了优化免疫方案和衡量其临床疗效的有前途的新方法。