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[衰老与神经退行性变:分子与细胞基础]

[Aging and neurodegeneration: molecular and cellular bases].

作者信息

Peinado M A, del Moral M L, Esteban F J, Martínez-Lara E, Siles E, Jiménez A, Hernández-Cobo R, Blanco S, Rodrigo J, Pedrosa J A

机构信息

Unidad Asociada CSIC-Universidad de Jaén, Areas de Biología Celular y Bioquímica y Biología Molecular, Departamento de Neuroanatomía Comparada, Madrid, España.

出版信息

Rev Neurol. 2000;31(11):1054-65.

Abstract

OBJECTIVE

A review about the possible cellular and molecular mechanisms of aging and related neurodegenerative diseases.

DEVELOPMENT

The mechanisms involved in neuronal decrease, connectivity losses and glial reactivity, detected both in neurodegenerative (Alzheimer's disease) and physiological aging, are analyzed from the morphological and histological point of view to provide the morphofunctional base of the cognitive and intellectual alterations characterizing the senescence process. Taken together, these data are correlated to the possible genetical aspects implied in this process, reviewing the most relevant results on senescence and cellular death obtained from yeast, fruit fly and nematodes; besides this, a brief review of the molecular biology of gerontogenes was carried out, and the possible mechanisms inducing aging and neurodegenerative processes are analyzed according to the state-of-the-art related theories. Finally, cellular, biochemical and genetical data are correlated in the signal transduction way implied in the increase of the intracellular calcium level as the starting point of cell death.

CONCLUSIONS

The main process implied in the neuronal cell death responsible for aging and the related neurodegenerative diseases are started by different agents such as the lacking of neurotrophic factors, hypoxia, hypoglycemia, excitotoxicity, and oxygen and nitrogen free radicals.

摘要

目的

综述衰老及相关神经退行性疾病可能的细胞和分子机制。

进展

从形态学和组织学角度分析了在神经退行性疾病(阿尔茨海默病)和生理性衰老中均检测到的神经元减少、连接丧失和胶质细胞反应性所涉及的机制,以提供表征衰老过程的认知和智力改变的形态功能基础。综合这些数据,将其与该过程中可能涉及的遗传方面相关联,回顾从酵母、果蝇和线虫中获得的关于衰老和细胞死亡的最相关结果;除此之外,对老年基因的分子生物学进行了简要综述,并根据最新相关理论分析了诱导衰老和神经退行性过程的可能机制。最后,将细胞、生化和遗传数据以细胞内钙水平升高作为细胞死亡起点所涉及的信号转导方式进行关联。

结论

导致衰老及相关神经退行性疾病的神经元细胞死亡所涉及的主要过程由不同因素引发,如神经营养因子缺乏、缺氧、低血糖、兴奋性毒性以及氧和氮自由基。

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