期刊
NEUROBIOLOGY OF AGING
卷 35, 期 1, 页码 96-108出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.07.001
关键词
Ambra1; Autophagy; Brain; Hippocampus; Neocortex; Neuron; Glia; Neurodegeneration; Aging; Alzheimer's disease; Tg2576
资金
- University Roma Tre (Internationalization and Research Training Project)
- University Roma Tre (CAL)
- Telethon Foundation [GGP10225]
- Italian Ministry of University and Research (FIRB)
- Italian Ministry of Health (Ricerca Finalizzata)
- Italian Ministry of Health (Ricerca Corrente)
- AIRC
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. (c) 2014 Elsevier Inc. All rights reserved.
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