阿尔茨海默病的病理生理方面和治疗手段:近期趋势和未来发展。

IF 3.6 4区 医学 Q3 CELL BIOLOGY Cellular and Molecular Neurobiology Pub Date : 2023-11-01 Epub Date: 2023-09-19 DOI:10.1007/s10571-023-01408-7
Bhavarth P Dave, Yesha B Shah, Kunal G Maheshwari, Kaif A Mansuri, Bhadrawati S Prajapati, Humzah I Postwala, Mehul R Chorawala
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引用次数: 1

摘要

阿尔茨海默病(AD)是痴呆症的主要原因,其特征是由于不溶性淀粉样蛋白斑块的积累、tau蛋白的过度磷酸化以及细胞内神经原纤维缠结的形成而导致脑细胞死亡。AD还与其他病理有关,如神经炎症、突触连接和回路功能障碍、线粒体功能和能量产生障碍、表观遗传变化和血管系统异常。尽管在过去的一百年里进行了广泛的研究,但关于AD的病因或如何有效治疗,却知之甚少。鉴于疾病的严重性和受影响人数的不断增加,迫切需要发现有效的AD药物。自2003年以来,美国食品药品监督管理局(FDA)已经批准了几种用于AD管理的新药分子,但这些药物只是暂时缓解症状,并没有解决疾病的根本原因。目前,可用的药物专注于纠正AD中观察到的神经递质破坏,包括胆碱酯酶抑制剂和N-甲基-D-天冬氨酸(NMDA)受体拮抗剂,它可以暂时缓解痴呆的症状,但不能预防或逆转AD的进程。目前正在进行改性AD治疗的研究,包括基因治疗,脂质纳米颗粒和基于树枝状聚合物的治疗。这些创新方法旨在针对AD的潜在病理过程,而不仅仅是管理症状。这篇综述讨论了与AD病因有关的发病机制的新方面,以及治疗AD的治疗药物的最新进展,如基因治疗、脂质纳米颗粒和基于树枝状聚合物的治疗等。
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Pathophysiological Aspects and Therapeutic Armamentarium of Alzheimer's Disease: Recent Trends and Future Development.

Alzheimer's disease (AD) is the primary cause of dementia and is characterized by the death of brain cells due to the accumulation of insoluble amyloid plaques, hyperphosphorylation of tau protein, and the formation of neurofibrillary tangles within the cells. AD is also associated with other pathologies such as neuroinflammation, dysfunction of synaptic connections and circuits, disorders in mitochondrial function and energy production, epigenetic changes, and abnormalities in the vascular system. Despite extensive research conducted over the last hundred years, little is established about what causes AD or how to effectively treat it. Given the severity of the disease and the increasing number of affected individuals, there is a critical need to discover effective medications for AD. The US Food and Drug Administration (FDA) has approved several new drug molecules for AD management since 2003, but these drugs only provide temporary relief of symptoms and do not address the underlying causes of the disease. Currently, available medications focus on correcting the neurotransmitter disruption observed in AD, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate (NMDA) receptor, which temporarily alleviates the signs of dementia but does not prevent or reverse the course of AD. Research towards disease-modifying AD treatments is currently underway, including gene therapy, lipid nanoparticles, and dendrimer-based therapy. These innovative approaches aim to target the underlying pathological processes of AD rather than just managing the symptoms. This review discusses the novel aspects of pathogenesis involved in the causation of AD of AD and in recent developments in the therapeutic armamentarium for the treatment of AD such as gene therapy, lipid nanoparticles, and dendrimer-based therapy, and many more.

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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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