Therapeutic Targeting of Autophagy in Alzheimer’s Disease

As terminally differentiated nervous system cells, neurons may be specialized to fight viral infections without undergoing cellular selfdestruction. Autophagy, the cellular lysosomal degradation pathway, is emerging as one such mechanisms of neuronal antiviraldefense. Autophagy has diverse physiological functions in cells, such as cellular adaptation to stress, routine organelle and protein turnover, and innate immunity against intracellular pathogens, including viruses. Much evidence for an antiviral role of autophagy is related to viruses that specifically target neurons, including the prototype alphavirus, Sindbis virus and the alpha-herpesvirus,herpes simplex virus type1 (HSV-1). Autophagy acts as both an anti-viral and pro-viral pathway in the nervous cells, and the roles of autophagy depend on the virus, the cell type and the cellular environment. Autophagy is the very important mechanism in preventing neurodegeneration, and induced autophagy is essential for promoting cellular survival, viral antagonism of autophagy in neurons may lead to neuronal dysfunction and/or neuronal cell death in patients. Autophagic control of inflammation is one area where this pathway may have similar benefits for both infectiousand neurodegenerative diseases beyond direct removal of the pathogenic agents. Alzheimer’s disease (AD) is a neurodegenerative disorderthat characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in thehippocampus and cortex. Many studies in recent yearswere showed significant associations between AD andvarious pathogens, specially Herpes simplex virustype 1(HSV-1). This review provides backgroundinformation on the roles of autophagy in immunity andneuroprotection, and then discusses about the therapeutictargeting of autophagy in Alzheimer’s disease.