COVID-19 was rapidly declared a pandemic by the World Health Organization, only three months after the initial outbreak in Wuhan, China. Early clinical care mainly focused on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are also emerging. To determine whether SARS-CoV-2 could target the human brain, we infected iPSC-derived human brain organoids. Our findings show that SARS-CoV-2 was able to infect and kill neural cells, including cortical neurons. This phenotype was accompanied by impaired synaptogenesis. Finally, Sofosbuvir, an FDA-approved antiviral drug, was able to rescue these alterations. Given that there are currently no vaccine or antiviral treatments available, urgent therapies are needed. Our findings put Sofosbuvir forward as a potential treatment to alleviate COVID-19-related neurological symptoms.One Sentence Summary: SARS-CoV-2 infection causes neuronal death and impaired synaptogenesis, both rescued by Sofosbuvir treatment.
One of the major developments that resulted from the human genome sequencing projects was a better understanding of the role of non-coding RNAs (ncRNAs). NcRNAs are divided into several different categories according to size and function; however, one shared feature is that they are not translated into proteins. In this review, we will discuss relevant aspects of ncRNAs, focusing on two main types: i) microRNAs, which negatively regulate gene expression either by translational repression or target mRNA degradation, and ii) small interfering RNAs (siRNAs), which are involved in the biological process of RNA interference (RNAi). Our knowledge regarding these two types of ncRNAs has increased dramatically over the past decade, and they have a great potential to become therapeutic alternatives for a variety of human conditions.
Epilepsy is misdiagnosed in up to 25% of patients, leading to serious and long-lasting consequences. Recently, circulating microRNAs have emerged as potential biomarkers in a number of clinical scenarios. The purpose of this study was to identify and to validate circulating microRNAs that could be used as biomarkers in the diagnosis of epilepsy. Quantitative real-time PCR was used to measure plasma levels of three candidate microRNAs in two phases of study: an initial discovery phase with 14 patients with mesial temporal lobe epilepsy (MTLE), 13 with focal cortical dysplasia (FCD) and 16 controls; and a validation cohort constituted of an independent cohort of 65 patients with MTLE and 83 controls. We found hsa-miR-134 downregulated in patients with MTLE (p = 0.018) but not in patients with FCD, when compared to controls. Furthermore, hsa-miR-134 expression could be used to discriminate MTLE patients with an area under the curve (AUC) of 0.75. To further assess the robustness of hsa-miR-134 as a biomarker for MTLE, we studied an independent cohort of 65 patients with MTLE, 27 of whom MTLE patients were responsive to pharmacotherapy, and 38 patients were pharmacoresistant and 83 controls. We confirmed that hsa-miR-134 was significantly downregulated in the plasma of patients with MTLE when compared with controls (p < 0.001). In addition, hsa-miR-134 identified patients with MTLE regardless of their response to pharmacotherapy or the presence of MRI signs of hippocampal sclerosis. We revealed that decreased expression of hsa-miR-134 could be a potential non-invasive biomarker to support the diagnosis of patients with MTLE.
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