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脑源性神经营养因子信号在阿尔茨海默病发病机制中的作用:黄酮类化合物的神经保护有益作用。

Brain-Derived Neurotrophic Factor Signaling in the Pathophysiology of Alzheimer's Disease: Beneficial Effects of Flavonoids for Neuroprotection.

机构信息

Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.

Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, Ibaraki 305-8566, Japan.

出版信息

Int J Mol Sci. 2021 May 27;22(11):5719. doi: 10.3390/ijms22115719.

Abstract

The function of the brain-derived neurotrophic factor (BDNF) via activation through its high-affinity receptor Tropomyosin receptor kinase B (TrkB) has a pivotal role in cell differentiation, cell survival, synaptic plasticity, and both embryonic and adult neurogenesis in central nervous system neurons. A number of studies have demonstrated the possible involvement of altered expression and action of the BDNF/TrkB signaling in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). In this review, we introduce an essential role of the BDNF and its downstream signaling in neural function. We also review the current evidence on the deregulated the BDNF signaling in the pathophysiology of AD at gene, mRNA, and protein levels. Further, we discuss a potential usefulness of small compounds, including flavonoids, which can stimulate BDNF-related signaling as a BDNF-targeting therapy.

摘要

脑源性神经营养因子(BDNF)通过其高亲和力受体原肌球蛋白受体激酶 B(TrkB)的激活发挥作用,在中枢神经系统神经元的细胞分化、细胞存活、突触可塑性以及胚胎和成年神经发生中起着关键作用。许多研究表明,BDNF/TrkB 信号转导的表达和功能改变可能与神经退行性疾病的发病机制有关,包括阿尔茨海默病(AD)。在这篇综述中,我们介绍了 BDNF 及其下游信号转导在神经功能中的重要作用。我们还回顾了目前关于 BDNF 信号转导在 AD 病理生理学中基因、mRNA 和蛋白质水平失调的证据。此外,我们还讨论了一些小分子化合物的潜在用途,包括类黄酮,它们可以刺激与 BDNF 相关的信号转导,作为 BDNF 靶向治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbb/8199014/3aeda5ef347c/ijms-22-05719-g001.jpg

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