Enteroviral Infection: The Forgotten Link to Amyotrophic Lateral Sclerosis?

Frontiers in Molecular Neuroscience

Honglin Luo²  Yuan Chao Xue²  Neil Cashman³  Ralph Feuer⁴ 

[1] Centre for Heart and Lung Innovation, University of British Columbia, Vancouver, BC, Canada;Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada;The Integrated Regenerative Research Institute at San Diego State University, San Diego, CA, United States;

关键词: amyotrophic lateral sclerosis;    enterovirus;    TDP-43 pathology;    nucleocytoplasmic trafficking;    RNA metabolism;    autophagy;   

DOI  :  10.3389/fnmol.2018.00063

来源: DOAJ

【 摘 要 】

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that primarily attacks motor neurons in the brain and spinal cord, leading to progressive paralysis and ultimately death. Currently there is no effective therapy. The majority of ALS cases are sporadic, with no known family history; unfortunately the etiology remains largely unknown. Contribution of Enteroviruses (EVs), a family of positive-stranded RNA viruses including poliovirus, coxsackievirus, echovirus, enterovirus-A71 and enterovirus-D68, to the development of ALS has been suspected as they can target motor neurons, and patients with prior poliomyelitis show a higher risk of motor neuron disease. Multiple efforts have been made to detect enteroviral genome in ALS patient tissues over the past two decades; however the clinical data are controversial and a causal relationship has not yet been established. Recent evidence from in vitro and animal studies suggests that enterovirus-induced pathology remarkably resembles the cellular and molecular phenotype of ALS, indicating a possible link between enteroviral infection and ALS pathogenesis. In this review, we summarize the nature of enteroviral infection, including route of infection, cells targeted, and viral persistence within the central nervous system (CNS). We review the molecular mechanisms underlying viral infection and highlight the similarity between viral pathogenesis and the molecular and pathological features of ALS, and finally, discuss the potential role of enteroviral infection in frontotemporal dementia (FTD), a disease that shares common clinical, genetic, and pathological features with ALS, and the significance of anti-viral therapy as an option for the treatment of ALS.

【 授权许可】

Unknown