纳米线脑溶蛋白和单克隆淀粉样蛋白β肽抗体与5-羟色胺5-HT6受体拮抗剂SB-399885联合给药可阻止应激诱导的阿尔茨海默病脑病理恶化。

International review of neurobiology Pub Date : 2023-01-01 Epub Date: 2023-09-16 DOI:10.1016/bs.irn.2023.05.018
Hari Shanker Sharma, Lianyuan Feng, Dafin F Muresanu, Z Ryan Tian, José Vicente Lafuente, Anca D Buzoianu, Ala Nozari, Igor Bryukhovetskiy, Igor Manzhulo, Lars Wiklund, Aruna Sharma
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引用次数: 0

摘要

阿尔茨海默病是影响全世界人类的毁灭性神经退行性疾病之一,年龄增长主要在65岁及以上,给生活带来巨大痛苦。2023年,美国约有700多万人患有阿尔茨海默病,这给医疗保健系统、护理人员和家庭支持带来了巨大负担。然而,目前还没有合适的治疗措施来提高这些患者的生活质量。阿尔茨海默病的发展可能反映了整个生活的压力负担,灌输了这些中枢神经系统神经退行性疾病的疾病过程。因此,在探索阿尔茨海默病脑病理中的神经保护作用时,需要使用包括抗体在内的合适药物治疗的纳米递送的新策略。在本章中,基于我们自己的研究,探讨了压力在加剧阿尔茨海默病脑病理中的作用,并使用纳米技术研究了治疗策略。我们的观察清楚地表明,约束应激显著加剧了阿尔茨海默病的大脑病理,多模式药物脑磷脂与淀粉样蛋白β肽(aβP)单克隆抗体(mAb)以及5-羟色胺5-HT6受体拮抗剂SB3999885的纳米递送显著阻断了由约束应激加剧的阿尔茨海默病大脑病理,之前未报告。讨论了可能的机制和未来的临床意义。
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Stress induced exacerbation of Alzheimer's disease brain pathology is thwarted by co-administration of nanowired cerebrolysin and monoclonal amyloid beta peptide antibodies with serotonin 5-HT6 receptor antagonist SB-399885.

Alzheimer's disease is one of the devastating neurodegenerative diseases affecting mankind worldwide with advancing age mainly above 65 years and above causing great misery of life. About more than 7 millions are affected with Alzheimer's disease in America in 2023 resulting in huge burden on health care system and care givers and support for the family. However, no suitable therapeutic measures are available at the moment to enhance quality of life to these patients. Development of Alzheimer's disease may reflect the stress burden of whole life inculcating the disease processes of these neurodegenerative disorders of the central nervous system. Thus, new strategies using nanodelivery of suitable drug therapy including antibodies are needed in exploring neuroprotection in Alzheimer's disease brain pathology. In this chapter role of stress in exacerbating Alzheimer's disease brain pathology is explored and treatment strategies are examined using nanotechnology based on our own investigation. Our observations clearly show that restraint stress significantly exacerbate Alzheimer's disease brain pathology and nanodelivery of a multimodal drug cerebrolysin together with monoclonal antibodies (mAb) to amyloid beta peptide (AβP) together with a serotonin 5-HT6 receptor antagonist SB399885 significantly thwarted Alzheimer's disease brain pathology exacerbated by restraint stress, not reported earlier. The possible mechanisms and future clinical significance is discussed.

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