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纳米载体递送抗 tau 和神经元型一氧化氮合酶与脑活素联合应用可减轻创伤性脑损伤诱导的帕金森病脑病理恶化。

Nanowired delivery of antibodies to tau and neuronal nitric oxide synthase together with cerebrolysin attenuates traumatic brain injury induced exacerbation of brain pathology in Parkinson's disease.

机构信息

Dept. Biomedical Engineering, University of Arkansas, Fayetteville, AR, United Staes.

International Experimental Central Nervous System Injury & Repair (IECNSIR), Dept. of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden.

出版信息

Int Rev Neurobiol. 2023;171:83-121. doi: 10.1016/bs.irn.2023.07.001. Epub 2023 Sep 15.

DOI:10.1016/bs.irn.2023.07.001
PMID:37783564
Abstract

Concussive head injury (CHI) is one of the major risk factors for developing Parkinson's disease in later life of military personnel affecting lifetime functional and cognitive disturbances. Till date no suitable therapies are available to attenuate CHI or PD induced brain pathology. Thus, further exploration of novel therapeutic agents are highly warranted using nanomedicine in enhancing the quality of life of veterans or service members of US military. Since PD or CHI induces oxidative stress and perturbs neurotrophic factors regulation associated with phosphorylated tau (p-tau) deposition, a possibility exists that nanodelivery of agents that could enhance neurotrophic factors balance and attenuate oxidative stress could be neuroprotective in nature. In this review, nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies to neuronal nitric oxide synthase (nNOS) with p-tau antibodies was examined in PD following CHI in model experiments. Our results suggest that combined administration of nanowired antibodies to nNOS and p-tau together with cerebrolysin significantly attenuated CHI induced exacerbation of PD brain pathology. This combined treatment also has beneficial effects in CHI or PD alone, not reported earlier.

摘要

脑震荡性头部损伤(CHI)是影响军人晚年生活的帕金森病的主要危险因素之一,导致终生功能和认知障碍。迄今为止,尚无合适的疗法可减轻 CHI 或 PD 引起的脑病理学改变。因此,使用纳米医学进一步探索新型治疗剂来提高美国军人的生活质量是非常必要的。由于 PD 或 CHI 会引起氧化应激并扰乱与磷酸化 tau(p-tau)沉积相关的神经营养因子调节,因此存在这样一种可能性,即纳米传递能够增强神经营养因子平衡和减轻氧化应激的药物可能具有神经保护作用。在本综述中,在模型实验中检查了神经细胞营养因子和活性肽片段的平衡组成与神经元型一氧化氮合酶(nNOS)的单克隆抗体与 p-tau 抗体的脑活素的纳米线传递在 CHI 后 PD 中的作用。我们的结果表明,纳米线传递的 nNOS 和 p-tau 与脑活素联合给药可显著减轻 CHI 引起的 PD 脑病理学恶化。这种联合治疗在 CHI 或 PD 中也有单独治疗没有报告过的有益作用。

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