Neuroinflammation links COVID-19 and fragile X syndrome: Role of MMP-9, IGF-1, IL-10, metformin, statins and curcumin

Abstract

There is no existing specific treatment for COVID-19, so it is imperative to understand the pathophysiological pathways for the development of successful treatment. SARS-CoV-2 infection leads to the release of inflammatory cytokines which can result in an excessive inflammatory reaction or cytokine storm leading to worsening prognosis. These processes are mediated by several signalling pathways such us PI3K/Akt/mTOR and Ras/MAPK/ERK cascades, \xa0GSK-3 kinase, and NF-kB. In fragile X syndrome (FXS), the most common cause of inherited mental retardation and the most common genetic form of autism spectrum disorder, those signalling pathways as well as IGF-1 are upregulated, leading to increase of metalloproteinase 9 (MMP-9) levels, tissue damage, pro-inflammatory state and blood-brain barrier disruption. The number of links found between FXS and COVID-19 suggests they share pathophysiological mechanisms. FXS would be an important risk factor for developing a severe form of COVID-19 and in turn, SARS-CoV-2 could contribute to worsening the symptoms and prognosis of patients with FXS as well as asymptomatic Fmr1 premutation carriers. These asymptomatic individuals could explain a proportion of the COVID-19 cases that, without other underlying pathologies, develop cytokine storm and severe disease. With all the above, deep study of these processes that involve both FXS and COVID-19, would facilitate the discovery of potential therapeutic targets and drug development for these diseases. The potential mechanisms of metformin, trofinetide, statins, curcumin and IL-10 affecting different points of these ways are discussed further here.