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成人脑室下区神经发生与阿尔茨海默病的关系:病理作用及治疗意义

Relationship between adult subventricular neurogenesis and Alzheimer's disease: Pathologic roles and therapeutic implications.

作者信息

Kim Hyeon Soo, Shin Seong Min, Kim Sujin, Nam Yunkwon, Yoo Anji, Moon Minho

机构信息

Department of Biochemistry, College of Medicine, Konyang University, Daejeon, South Korea.

Research Institute for Dementia Science, Konyang University, Daejeon, South Korea.

出版信息

Front Aging Neurosci. 2022 Sep 14;14:1002281. doi: 10.3389/fnagi.2022.1002281. eCollection 2022.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by irreversible cognitive declines. Senile plaques formed by amyloid-β (Aβ) peptides and neurofibrillary tangles, consisting of hyperphosphorylated tau protein accumulation, are prominent neuropathological features of AD. Impairment of adult neurogenesis is also a well-known pathology in AD. Adult neurogenesis is the process by which neurons are generated from adult neural stem cells. It is closely related to various functions, including cognition, as it occurs throughout life for continuous repair and development of specific neural pathways. Notably, subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, transports neurons to several brain regions such as the olfactory bulb, cerebral cortex, striatum, and hippocampus. These migrating neurons can affect cognitive function and behavior in different neurodegenerative diseases. Despite several studies indicating the importance of adult SVZ neurogenesis in neurodegenerative disorders, the pathological alterations and therapeutic implications of impaired adult neurogenesis in the SVZ in AD have not yet been fully explained. In this review, we summarize recent progress in understanding the alterations in adult SVZ neurogenesis in AD animal models and patients. Moreover, we discuss the potential therapeutic approaches for restoring impaired adult SVZ neurogenesis. Our goal is to impart to readers the importance of adult SVZ neurogenesis in AD and to provide new insights through the discussion of possible therapeutic approaches.

摘要

阿尔茨海默病(AD)是一种以不可逆认知衰退为特征的神经退行性疾病。由淀粉样β(Aβ)肽形成的老年斑以及由过度磷酸化的tau蛋白积累构成的神经原纤维缠结是AD突出的神经病理学特征。成体神经发生受损也是AD中一种众所周知的病理现象。成体神经发生是指成年神经干细胞产生神经元的过程。它与包括认知在内的各种功能密切相关,因为它在整个生命过程中持续进行,以不断修复和发育特定的神经通路。值得注意的是,发生在侧脑室的脑室下区(SVZ)神经发生会将神经元输送到几个脑区,如嗅球、大脑皮层、纹状体和海马体。这些迁移的神经元会影响不同神经退行性疾病中的认知功能和行为。尽管有几项研究表明成体SVZ神经发生在神经退行性疾病中的重要性,但AD中SVZ成体神经发生受损的病理改变和治疗意义尚未得到充分解释。在这篇综述中,我们总结了在理解AD动物模型和患者中SVZ成体神经发生改变方面的最新进展。此外,我们讨论了恢复受损的成体SVZ神经发生的潜在治疗方法。我们的目标是让读者了解成体SVZ神经发生在AD中的重要性,并通过讨论可能的治疗方法提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ad8/9518691/84e04b3df48e/fnagi-14-1002281-g001.jpg

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