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谷氨酸脱氢酶的谐波活性与神经可塑性:对衰老、认知功能障碍和神经退行性变的影响。

Harmonic activity of glutamate dehydrogenase and neuroplasticity: The impact on aging, cognitive dysfunction, and neurodegeneration.

作者信息

Salarvandian Shakiba, Digaleh Hadi, Khodagholi Fariba, Javadpour Pegah, Asadi Sareh, Zaman Amir Ali Orang, Dargahi Leila

机构信息

Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Neurosurgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Behav Brain Res. 2025 Mar 5;480:115399. doi: 10.1016/j.bbr.2024.115399. Epub 2024 Dec 13.

Abstract

In recent years, glutamate has attracted significant attention for its roles in various brain processes. However, one of its key regulators, glutamate dehydrogenase (GDH), remains understudied despite its pivotal role in several biochemical pathways. Dysfunction or dysregulation of GDH has been implicated in aging and various neurological disorders, such as Alzheimer's disease and Parkinson's disease. In this review, the impact of GDH on aging, cognitive impairment, and neurodegenerative conditions, as exemplars of the phenomena that may affected by neuroplasticity, has been reviewed. Despite extensive research on synaptic plasticity, the precise influence of GDH on brain structure and function remains undiscovered. This review of existing literature on GDH and neuroplasticity reveals diverse and occasionally conflicting effects. Future research endeavors should aim to describe the precise mechanisms by which GDH influences neuroplasticity (eg. synaptic plasticity and neurogenesis), particularly in the context of human aging and disease progression. Studies on GDH activity have been limited by factors such as insufficient sample sizes and varying experimental conditions. Researchers should focus on investigating the molecular mechanisms by which GDH modulates neuroplasticity, utilizing various animal strains and species, ages, sexes, GDH isoforms, brain regions, and cell types. Understanding GDH's role in neuroplasticity may offer innovative therapeutic strategies for neurodegenerative and psychiatric diseases, potentially slowing the aging process and promoting brain regeneration.

摘要

近年来,谷氨酸因其在各种脑过程中的作用而备受关注。然而,其关键调节因子之一谷氨酸脱氢酶(GDH),尽管在多个生化途径中起关键作用,但仍未得到充分研究。GDH的功能障碍或失调与衰老及各种神经疾病有关,如阿尔茨海默病和帕金森病。在本综述中,我们回顾了GDH对衰老、认知障碍和神经退行性疾病的影响,这些是可能受神经可塑性影响的现象的典型例子。尽管对突触可塑性进行了广泛研究,但GDH对脑结构和功能的精确影响仍未被发现。这篇对现有关于GDH和神经可塑性文献的综述揭示了多样且偶尔相互矛盾的影响。未来的研究应旨在描述GDH影响神经可塑性(如突触可塑性和神经发生)的精确机制,特别是在人类衰老和疾病进展的背景下。对GDH活性的研究受到样本量不足和实验条件各异等因素的限制。研究人员应专注于利用各种动物品系和物种、年龄、性别、GDH亚型、脑区和细胞类型,研究GDH调节神经可塑性的分子机制。了解GDH在神经可塑性中的作用可能为神经退行性疾病和精神疾病提供创新的治疗策略,有可能延缓衰老过程并促进脑再生。

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