HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

An insight into the role of autophagy in cell responses in the aging and neurodegenerative brain

B. Caballero1 and A. Coto-Montes2

1Department of Molecular Pharmacology, The Bruce Rappaport Faculty of Medicine, Israel Institute of Technology-Technion, Haifa, Israel and 2Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.

Offprint requests to: Dr. Ana Coto-Montes, Departamento de Morfología y Biología Celular , Facultad de Medicina, C/ Julián Clavería s/n, 33006, Oviedo, Spain. e-mail: acoto@uniovi.es


Summary. Oxidative stress, inflammation and the aggregation of oxidized, misfolded or aberrant proteins in the brain induces deregulations in programmed cell death: apoptosis and autophagy. Apoptosis is one of processes implicated in aging and neurodegenerative pathologies, and for the last decade, has been one of the most studied processes due to its essential role, not only in aging, but also in many neurodegenerative diseases, including Parkinson’s, Alzheimer’s and Huntington’s. However, autophagy being the major intracellular pathway for the degradation and recycling of long-live proteins and organelles is widely involved in the pathogenesis or prevention of many age-related diseases, including neurodegenerative conditions. Recently, autophagy activation has been considered as part of the cellular responses to elevated oxidative stress, eliminating unwanted, damaged and oxidative structures; thus favouring, in this way, the key anti-aging mechanism associated with the caloric restriction. Longevity factors, such as sirtuins, and redox-sensitive transcriptional factors, such as NF-κB and p53, can also regulate basal autophagy in cells, with a direct impact on longevity and the development of inflammation and neurodegeneration. Here, we reviewed the critical changes of autophagy in the aging and neuro-degenerative brain and the role of key regulators of autophagy, which are directly related to oxidative stress, inflammation and longevity pathways
. Histol Histopathol 27, 263-275 (2012)

Key words: Neurodegeneration, Autophagy, Sirtuins, NF-κB, p53

DOI: 10.14670/HH-27.263