Autophagy and its neuroprotection in neurodegenerative diseases

It has been suggested that protein misfolding and aggregation contribute significantly to the development of neurodegenerative diseases.Misfolded and aggregated proteins are cleared by ubiquitin proteasomal system (UPS) and by both Micro and Macro autophagy lysosomal pathway (ALP).Autophagosomal dysfunction has been implicated in an increasing number of diseases including neurodegenerative diseases.Autophagy is a cellular self-eating process that plays an important role in neuroprotection as well as neuronal injury and death.While a decrease in autophagic activity interferes with protein degradation and possibly organelle turnover,increased autophagy has been shown to facilitate the clearance of aggregation-prone proteins and promote neuronal survival in a number of disease models.On the other hand,too much autophagic activity can be detrimental,suggesting the regulation of autophagy is critical in dictating cell fate.In this review paper,we will discuss various aspects of ALP biology and its dual functions in neuronal cell death and survival.We will also evaluate the role of autophagy in neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,amyotrophic lateral sclerosis.Finally,we will explore the therapeutic potential of autophagy modifiers in several neurodegenerative diseases.