Imbalance in production and clearance of amyloid beta (Aβ) is the primary reason for its deposition in Alzheimer disease. Macroautophagy/autophagy is one of the important mechanisms for clearance of both intracellular and extracellular Aβ. Here, through screening, we identified alborixin, an ionophore, as a potent inducer of autophagy. We found that autophagy induced by alborixin substantially cleared Aβ in microglia and primary neuronal cells. Induction of autophagy was accompanied by up regulation of autophagy proteins BECN1/Beclin 1, ATG5, ATG7 and increased lysosomal activities. Autophagy induced by alborixin was associated with inhibition of the phosphoinositide 3-kinase (PI3K)-AKT pathway. A knock down of PTEN and consistent, constitutive activation of AKT inhibited alborixin-induced autophagy and consequent clearance of Aβ. Furthermore, clearance of Aβ by alborixin led to significant reduction of Aβ-mediated cytotoxicity in primary neurons and differentiated N2a cells. Thus, our findings put forward alborixin as a potential anti-Alzheimer therapeutic lead.

The emergence of the global pandemic caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put a challenge to identify or derive the therapeutics for its prevention and treatment. Despite the unprecedented advances in the modern medicinal system, currently, there are no proven effective therapies. However, rapid research on SARS-CoV-2 epidemiology help unveiling some new targets for potential drug therapies. Many drugs have been screened, and even their clinical trials are going on at an exceptional pace. Amongst these RNA-dependent RNA polymerase inhibitors (favipiravir and remdesivir) and steroids especially dexamethasone showed promising effects. The biological agents like tocilizumab, interferons, and convalescent plasma prove to be beneficial in viral clearance. Moreover, many immunomodulatory and viral S protein targeting vaccines have their ongoing clinical trials. The establishment of various in vitro and in vivo models for preclinical studies can additionally help the current research. The volume and the pace of the clinical trials launched to evaluate the safety and efficacy of various agents against coronavirus disease 2019 (COVID-19) reflect the need for high-quality evidence for various therapies to be practiced by clinicians. This study aims to sum up all the current advances in the global medicinal system against the COVID-19.

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