Exogenous and Endogenous Virus Infection and Pollutants Drive Neuronal Cell Senescence and Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease causing the most frequent form of dementia in old age. AD etiology is still uncertain and deposition of abnormal proteins in the brain along with chronic neuroinflammation have been suggested as pathogenic mechanisms of neuronal death. Infections by exogenous neurotropic virus, endogenous retrovirus reactivation, infections by other microbes, and air pollutants may either induce neurodegeneration or activate brain inflammation. Up to 8% of the human genome has a retroviral origin. These ancient retroviruses, also called human endogenous retroviruses, are associated with a clinical history of several neurodegenerative diseases. Under persistent stress, such as chronic infections and inflammation, neurons, and microglia cells may enter a state of division inactivation called cell senescence. Senescent cells are resistant to apoptosis and can release pro-inflammatory molecules promoting the functional decline of tissues and organs and also activate silent viruses. Infections and mutations induced by pollutants can lead to the expression of different endogenous retroviruses, which may contribute to several different diseases, including AD-associated neurodegeneration. Here I discuss that infection by exogenous pathogen, activation of endogenous retrovirus or retrotransposons and pollutants might induce neuronal senescence and cause persistent brain neurodegeneration. Therefore, cell senescence appears to be an emerging mechanism that might contribute to AD neurodegeneration. Finally, treatment of AD patients with senolytic drugs, e.g., compounds able to kill senescent cells, might show a positive effect on AD progression.