title: Understanding risk factors for Alzheimer's disease: interplay of neuroinflammation, connexin-based communication and oxidative stress.
abstract: Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by dementia and the presence of amyloid plaques and anomalous tau aggregates. Although pathophysiological mechanisms are still unclear, neuroinflammation and glial cell dysfunction have been identified as conspicuous components of AD. Glial cell dysfunction is associated with dysregulated production of inflammation mediators and generation of both reactive oxygen species (ROS) and reactive nitrogen species (RNS), which affect synapses and induce neuronal damage. Importantly, both increased neuroinflammation and ROS/RNS production by glia dysregulate communication mediated by connexin-based channels in brain cells, which could further affect oxidative balance and neuronal viability. Recent evidence suggests that connexin-based channels could be involved in AD pathogenesis. Here we discuss how aging affects neuroinflammation, oxidative stress, and connexin-based channels and the potential relevance of these changes for AD. Understanding how they cooperate as pathogenic mechanisms of AD is promising for the discovery of new therapeutic strategies against neurodegenerative disorders.
authors.affiliation: Departamento de Neurología, Laboratorio de Neurociencias, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Quintanilla
authors.forename: Juan A
authors.initials: JA
authors.lastname: Orellana
authors.forename: Rommy
authors.initials: R
authors.lastname: von Bernhardi
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D012307:Risk Factors; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017630:Connexins; D016875:tau Proteins