The role of Bcl-2 proteins in modulating neuronal Ca(2+) signaling in health and in Alzheimer's disease.

The role of Bcl-2 proteins in modulating neuronal Ca(2+) signaling in health and in Alzheimer's disease.
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DOI:
10.1016/j.bbamcr.2021.118997
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发表时间:
2021-05
期刊:
Biochimica et biophysica acta. Molecular cell research
影响因子:
--
通讯作者:
Vervliet T
Vervliet T
中科院分区:
其他
文献类型:
--
作者:
Callens M;Kraskovskaya N;Derevtsova K;Annaert W;Bultynck G;Bezprozvanny I;Vervliet T

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B 细胞淋巴瘤 2 (Bcl-2) 蛋白家族在细胞健康中发挥着关键功能。 Bcl-2 主要作用于线粒体,控制细胞凋亡的启动。然而,在过去的几十年中,人们已经清楚该蛋白家族还参与控制细胞中的 Ca2+ 信号传导,这是大多数细胞类型(包括神经元)功能的关键过程。一些抗凋亡和促凋亡的 Bcl-2 家族成员在神经元中表达并影响神经元功能。重要的是,神经元 Bcl-2 蛋白的表达水平受年龄影响。在这篇综述中,我们重点关注 Bcl-2 蛋白在神经元细胞中的新作用。具体来说,我们讨论了它们的失调如何导致阿尔茨海默病 (AD) 中神经退行性变的发生、发展和进展。异常的Ca2+信号在AD的发病机制中起着重要作用,我们提出Bcl-2-Ca2+信号轴的失调可能导致AD的进展,在此,Bcl-2可能构成AD治疗的潜在治疗靶点。
The family of B-cell lymphoma-2 (Bcl-2) proteins exerts key functions in cellular health. Bcl-2 primarily acts in mitochondria where it controls the initiation of apoptosis. However, during the last decades, it has become clear that this family of proteins is also involved in controlling Ca2+ signaling in cells, a critical process for the function of most cell types, including neurons. Several anti- and pro-apoptotic Bcl-2 family members are expressed in neurons and impact neuronal function. Importantly, expression levels of neuronal Bcl-2 proteins are affected by age. In this review, we focus on the emerging roles of Bcl-2 proteins in neuronal cells. Specifically, we discuss how their dysregulation contributes to the onset, development, and progression of neurodegeneration in the context of Alzheimer’s disease (AD). Aberrant Ca2+ signaling plays an important role in the pathogenesis of AD, and we propose that dysregulation of the Bcl-2-Ca2+ signaling axis may contribute to the progression of AD and that herein, Bcl-2 may constitute a potential therapeutic target for the treatment of AD.
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