Autophagic activity in neuronal cell death.

As post-mitotic cells with great energy demands, neurons depend upon the homeostatic and waste-recycling functions provided by autophagy. In addition, autophagy also promotes survival during periods of harsh stress and targets aggregate-prone proteins associated with neurodegeneration for degradation. Despite this, autophagy has also been controversially described as a mechanism of programmed cell death. Instances of autophagic cell death are typically associated with elevated numbers of cytoplasmic autophagosomes, which have been assumed to lead to excessive degradation of cellular components. Due to the high activity and reliance on autophagy in neurons, these cells may be particularly susceptible to autophagic death. In this review, we summarize and assess current evidence in support of autophagic cell death in neurons, as well as how the dysregulation of autophagy commonly seen in neurodegeneration can contribute to neuron loss. From here, we discuss potential treatment strategies relevant to such cell-death pathways.DCR is funded by a Wellcome Trust Principal Research Fellowship and the NIHR Biomedical Research Unit in Dementia at Addenbrooke’s Hospital. This review is supported by Plymouth University and Northcott Medical Foundation.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s12264-015-1528-