靶向淀粉样蛋白 β 蛋白和 α-突触核蛋白的单一和联合免疫疗法在类似路易体痴呆模型中的作用。
Effects of single and combined immunotherapy approach targeting amyloid β protein and α-synuclein in a dementia with Lewy bodies-like model.
机构信息
AFFiRiS AG, Vienna Biocenter, Vienna, Austria.
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
出版信息
Alzheimers Dement. 2019 Sep;15(9):1133-1148. doi: 10.1016/j.jalz.2019.02.002. Epub 2019 Aug 1.
INTRODUCTION
Immunotherapeutic approaches targeting amyloid β (Aβ) protein and tau in Alzheimer's disease and α-synuclein (α-syn) in Parkinson's disease are being developed for treating dementia with Lewy bodies. However, it is unknown if single or combined immunotherapies targeting Aβ and/or α-syn may be effective.
METHODS
Amyloid precursor protein/α-syn tg mice were immunized with AFFITOPEs® (AFF) peptides specific to Aβ (AD02) or α-syn (PD-AFF1) and the combination.
RESULTS
AD02 more effectively reduced Aβ and pTau burden; however, the combination exhibited some additive effects. Both AD02 and PD-AFF1 effectively reduced α-syn, ameliorated degeneration of pyramidal neurons, and reduced neuroinflammation. PD-AFF1 more effectively ameliorated cholinergic and dopaminergic fiber loss; the combined immunization displayed additive effects. AD02 more effectively improved buried pellet test behavior, whereas PD-AFF1 more effectively improved horizontal beam test; the combined immunization displayed additive effects.
DISCUSSION
Specific active immunotherapy targeting Aβ and/or α-syn may be of potential interest for the treatment of dementia with Lewy bodies.
简介
针对阿尔茨海默病中淀粉样蛋白 β（Aβ）蛋白和 tau，以及帕金森病中α-突触核蛋白（α-syn）的免疫治疗方法正在被开发用于治疗路易体痴呆。然而，尚不清楚针对 Aβ 和/或 α-syn 的单一或联合免疫疗法是否有效。
方法
淀粉样前体蛋白/α-syn tg 小鼠用 AFFITOPEs®（AFF）针对 Aβ（AD02）或 α-syn（PD-AFF1）的肽段及其组合进行免疫接种。
结果
AD02 更有效地降低了 Aβ 和 pTau 的负担；然而，联合治疗显示出一些相加作用。AD02 和 PD-AFF1 均能有效降低 α-syn，改善锥体神经元变性，并减少神经炎症。PD-AFF1 更有效地改善了胆碱能和多巴胺能纤维的丧失；联合免疫显示出相加作用。AD02 更有效地改善了埋藏药丸测试行为，而 PD-AFF1 更有效地改善了水平梁测试；联合免疫显示出相加作用。
讨论
针对 Aβ 和/或 α-syn 的特异性主动免疫疗法可能对治疗路易体痴呆具有潜在的意义。
Zotero 插件