Commentary on interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death

Abstract

Autophagy is a fundamental regulatory cellular mechanism, which enables cells to survive after a checked clearance of damaged organelles and proteins and a recycle of necessary molecules like amino acids and fatty acids to maintain homeostasis. There are a lot of factors able to influence autophagy in the states of health and disease. In the excellent review by Sahu et al.[2], the role of autophagy, its mechanisms, and its protective role against the attack of pathogens are well described. However, even more controversial aspects of autophagy are addressed: first some pathogens, such as herpes simplex viruses, coxsackievirus, listeria monocytogenes have developed strategies to circumvent autophagy-dependent activation of host immune response, then some bacteria have the ability to modify the gene transcriptional level of the autophagic process, both in terms of downgrading of autophagy-related genes, as in the case of Yersinia enterocolitica and Francisella tularensis [3] , and in terms of up regulation of autophagy-related genes: this mechanism favors a prolonged inflammation at the infection site and results in further injury to surrounding healthy tissues, causing brain matter degeneration.The proposed hypothesis that prolonged infections of the central nervous system (CNS) by neurotropic pathogens, if associated with underlying conditions, might play a role in the pathogenesis of neurodegenerative diseases and the connections between autophagy dysregulation and neurodegeneration are subjects of great interest in literature.Recent studies have demonstrated an intrinsic connection between selective autophagy impairment and neurodegenerative diseases, including Alzheimer's disease (AD) [4][5][6][7]