Autophagy Mechanisms for Brain Recovery. Keep It Clean, Keep It Alive

Abstract

Most neurological pathologies that afflict humans are associated with the abnormal accumulation and aggregation of specific proteins into the cytoplasm and with mitochondrial dysfunction. Neuronal health is sustained by the fine regulation of protein synthesis and organelle biogenesis and their degradation to ensure efficient turnover. Autophagy is a powerful process for removing such proteins and for maintaining mitochondrial homeostasis. Thus, the autophagic activation may play important roles in neuronal cell survival and neuronal function under both physiological and pathological conditions. It is well accepted that the loss of basal autophagy or imbalance of autophagic flux leads to neuronal death. Autophagosomes accumulate abnormally in affected neurons of several neurodegenerative diseases such as AD, HD, PD, as well as in brain and spinal cord trauma. Thus, knowledge of cross-talk between autophagy impairment and pathophysiological mechanisms is a prerequisite for successful therapeutic interventions in neurological disorders. This chapter summarizes current understanding of how autophagy perturbations may affect neuronal function contributing to neurodegeneration in chronic and acute brain pathologies.