探索葡萄糖代谢、胰岛素抵抗和神经退行性病理的相互作用:来自链脲佐菌素和低血糖体外模型的见解。

IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY
Edna Grünblatt, Cristine Marie Yde Ohki, G Angelika Schmitt-Böhrer, Peter Riederer, Susanne Walitza
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引用次数: 0

摘要

神经退行性疾病引起公众对健康的关注。最近的证据表明,到2050年,阿尔茨海默病(AD)患者将增加两倍。痴呆症诊断发病率的上升引起了人们对这种无法治愈的疾病的社会经济和情感影响的关注,这种疾病通过认知能力下降降低了生活质量。虽然遗传和环境因素可能导致其病因,但这些疾病背后的神经病理机制仍在研究中。一种是脑胰岛素抵抗(BIR),它与临床认知功能障碍有关,并与线粒体功能障碍、神经发生缺陷和细胞死亡有关。不仅限于神经退行性变,这些表型还与其他神经精神疾病有关。链脲佐菌素(STZ)是一种靶向胰腺β细胞的致糖尿病药物,可以在合适的模型中模拟BIR。从患者的神经影像学到体外方法,科学家们一直在努力从行为、分子和细胞水平上了解这些疾病的病理生理学。虽然动物模型对研究胰岛素抵抗的全身效应是有用的,但体外表型研究代表了研究分子和细胞方面的另一种选择。STZ和低血糖样情景已经成功地用于研究原代细胞培养(例如,神经母细胞瘤细胞)和来自多能干细胞(iPSCs)的患者特异性神经细胞系的神经退行性疾病。有趣的是,STZ治疗或低血糖样条件在培养皿中能够诱导AD的病理特征,如a β斑块沉积和Tau蛋白过度磷酸化。根据这篇综述,这些方法在理解神经精神疾病中代谢变化的分子和细胞含义方面显示出潜力。此外,这些模型可能有助于确定新的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring the interplay of glucose metabolism, insulin resistance, and neurodegenerative pathologies: insights from streptozotocin and hypoglycaemic in vitro models.

Neurodegenerative diseases raise public health concerns. Recent evidence indicates that Alzheimer's disease (AD) sufferers will triple by 2050. The rising incidence of dementia diagnoses raises concerns about the socio-economical and emotional impact of this uncurable illness, which reduces quality of life through cognitive decline. Although genetic and environmental factors may contribute to its aetiology, neuropathological mechanisms underlying these disorders are still under investigation. One is brain insulin resistance (BIR), which has been associated with clinical cognitive dysfunction and linked to mitochondrial dysfunction, neurogenesis deficits, and cell death. Not limited to neurodegeneration, these phenotypes have been associated with other neuropsychiatric disorders. Streptozotocin (STZ), a diabetes-causing drug that targets pancreatic β-cells, may imitate BIR in suitable models. From patients' neuroimaging to in vitro approaches, scientists have been striving to understand the pathophysiology of such disorders at the behavioural, molecular, and cellular levels. Although animal models are useful for studying insulin resistance's systemic effects, in vitro phenotypic research represents an alternative to study molecular and cellular aspects. STZ and hypoglycaemia-like scenarios have been successful for studying neurodegenerative disorders in primary cell culture (e.g., neuroblastoma cells) and patient-specific neural cell lines derived from pluripotent stem cells (iPSCs). Intriguingly, STZ treatment or hypoglycaemia-like conditions in a dish were able to induce AD pathological characteristics such Aβ plaque deposition and Tau protein hyperphosphorylation. Such approaches have shown potential in understanding molecular and cellular implications of metabolic changes in neuropsychiatric disorders, according to this review. Furthermore, these models may help identify novel treatment targets.

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来源期刊
Journal of Neural Transmission
Journal of Neural Transmission 医学-临床神经学
CiteScore
7.20
自引率
3.00%
发文量
112
审稿时长
2 months
期刊介绍: The investigation of basic mechanisms involved in the pathogenesis of neurological and psychiatric disorders has undoubtedly deepened our knowledge of these types of disorders. The impact of basic neurosciences on the understanding of the pathophysiology of the brain will further increase due to important developments such as the emergence of more specific psychoactive compounds and new technologies. The Journal of Neural Transmission aims to establish an interface between basic sciences and clinical neurology and psychiatry. It intends to put a special emphasis on translational publications of the newest developments in the field from all disciplines of the neural sciences that relate to a better understanding and treatment of neurological and psychiatric disorders.
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