Department of Sciences, University "Roma Tre", Rome, Italy; Department of Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
Neurobiol Aging. 2014 Jan;35(1):96-108. doi: 10.1016/j.neurobiolaging.2013.07.001. Epub 2013 Aug 2.
Autophagy is a major protein degradation pathway, essential for stress-induced and constitutive protein turnover. In nervous tissue, autophagy is constitutively active and crucial to neuronal survival. The efficiency of the autophagic pathway reportedly undergoes age-related decline, and autophagy defects are observed in neurodegenerative diseases. Since Ambra1 plays a fundamental role in regulating the autophagic process in developing nervous tissue, we investigated the expression of this protein in mature mouse brain and during physiological and Alzheimer type aging. The present study accomplished the first complete map of Ambra1 protein distribution in the various brain areas, and highlights differential expression in neuronal/glial cell populations. Differences in Ambra1 content are possibly related to specific neuronal features and properties, particularly concerning susceptibility to neurodegeneration. Furthermore, the analysis of Ambra1 expression in physiological and pathological brain aging supports important, though conflicting, functions of autophagy in neurodegenerative processes. Thus, novel therapeutic approaches, based on autophagy modulation, should also take into account the age-dependent roles of this mechanism in establishing, promoting, or counteracting neurodegeneration.
自噬是一种主要的蛋白质降解途径，对应激诱导和组成性蛋白质周转至关重要。在神经组织中，自噬是组成性活跃的，对神经元存活至关重要。据报道，自噬途径的效率会随着年龄的增长而下降，并且在神经退行性疾病中观察到自噬缺陷。由于 Ambra1 在调节发育中的神经组织中的自噬过程中起着基础性作用，我们研究了这种蛋白质在成熟小鼠大脑中的表达以及在生理和阿尔茨海默氏型衰老过程中的表达。本研究完成了 Ambra1 蛋白在各种大脑区域中的分布的第一张完整图谱，并突出了神经元/神经胶质细胞群体中的差异表达。Ambra1 含量的差异可能与特定的神经元特征和特性有关，特别是与对神经变性的易感性有关。此外，对生理和病理性脑衰老中 Ambra1 表达的分析支持自噬在神经退行性过程中的重要（尽管存在冲突）作用。因此，基于自噬调节的新的治疗方法还应考虑到该机制在建立、促进或对抗神经退行性变中的年龄依赖性作用。
