Enterovirus infection and its relationship with neurodegenerative diseases

Figures

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  Fig. 1:. mechanisms leading to neurodegenerative diseases after virus infection. Virus infection can collectively trigger different alterations in cell processes through three main mechanisms: 1. It alters protein metabolism, perturbing protein synthesis and degradation (protein ubiquitination, degradation at the proteasome, and autophagy/aggrephagy). It also affects chaperon prevention/correction of protein misfolding. 2. Viruses can directly interact with proteins, leading to structural conversion, starting aggregation, and forming small toxic aggregates and amyloid fibrils. These fibrils can seed monomer aggregation, representing a self-replicating process. Different virus molecules, such as proteins, lipids, and nucleic acids, are supposed to show this property. 3. Viruses perturb post-translational protein modifications, modulating protein function and oligomerisation. For example, Tau hyperphosphorylation, associated with Alzheimer’s disease, can be triggered by a virus infection, leading to the formation of neurofibrillary tangles and cell dysfunction. This figure was designed at Biorender.com.

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  Fig. 2:. the potential effect of enterovirus (EV) infections in neural cells and its impact on developing neurodegenerative diseases (NDs). (A) After gaining access to the central nervous system (CNS), EV infects neural cells, leading to different alterations in cell processes and decreasing the number of neurons. (B) EV infection could stimulate neural cells to produce amyloid proteins as defense mechanisms, wrapping and neutralising the virus. These amyloid proteins constitute the amyloid plaques, which activate microglia releasing pro-inflammatory cytokines. (C) The blood-brain barrier (BBB) can be disturbed from outside the brain via peripheral inflammatory mediators and dysbiosis, as well as from within the brain by the mediators generated by neural cells that have been stimulated by EV infections.