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成年神经元的生存策略——踩下刹车

Adult neuron survival strategies--slamming on the brakes.

作者信息

Benn Susanna C, Woolf Clifford J

机构信息

Day Neuromuscular Research Lab, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA.

出版信息

Nat Rev Neurosci. 2004 Sep;5(9):686-700. doi: 10.1038/nrn1477.

Abstract

Developing neurons are programmed to die by an apoptotic pathway unless they are rescued by extrinsic growth factors that generate an anti-apoptotic response. By contrast, adult neurons need to survive for the lifetime of the organism, and their premature death can cause irreversible functional deficits. The default apoptotic pathway is shut down when development is complete, and consequently growth factors are no longer required to prevent death. To protect against accidental apoptotic cell death, anti-apoptotic mechanisms are activated in mature neurons in response to stress. Loss or reduced activity of these intrinsic anti-apoptotic 'brakes' might contribute to or accelerate neurodegeneration, whereas their activation might rescue neurons from injury or genetic abnormalities.

摘要

发育中的神经元被设定通过凋亡途径死亡,除非它们被能产生抗凋亡反应的外源性生长因子拯救。相比之下,成年神经元需要在生物体的整个生命周期中存活,它们的过早死亡会导致不可逆转的功能缺陷。当发育完成时,默认的凋亡途径会关闭,因此不再需要生长因子来防止细胞死亡。为了防止意外的凋亡性细胞死亡,成熟神经元会在应激反应中激活抗凋亡机制。这些内在抗凋亡“刹车”的缺失或活性降低可能会导致或加速神经退行性变,而它们的激活可能会使神经元免受损伤或遗传异常的影响。

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