Insights into role of microRNA in Alzheimer's disease: From contemporary research to bedside perspective.

One of the most prevalent neurodegenerative disorders is Alzheimer's disease (AD). Despite the pervasiveness of AD being considerable, the rates of both diagnosis and therapy are comparatively less and still lacking. For the treatment of AD, acetylcholinesterase inhibitors and NMDA receptor antagonists (Memantine) have received clinical approval. The approved drugs are only capable of mitigating the symptoms; however, halting the progression of the disease remains a matter of substantial concern. MicroRNAs (miRs) are a subclass of non-coding single-stranded RNA molecules that target mRNAs to control the expression of genes in certain tissues. Dysregulation in the expression and function of miRs contributes to a neurodegeneration-like pathogenesis seen in Alzheimer's disease (AD), featuring hallmark characteristics such as Aß aggregation, hyper-phosphorylation of Tau proteins, mitochondrial dysfunction, neuroinflammation, and apoptosis. These factors collectively underpin the cognitive deterioration and learning disabilities associated with AD. According to the research, numerous miRs have considerably different expression patterns in AD patients compared to healthy people. Due to these attributes, miRs prove to be effective diagnostic and therapeutic agents for AD. This review will examine clinical and preclinical data concerning the potential of miRs as diagnostic and therapeutic agents, utilizing various techniques (such as miR antagonists or inhibitors, miR agonists or mimics, miR sponges, and miR antisense oligonucleotides) to target specific pathogenic mechanisms in AD.

Fisetin attenuates arsenic and fluoride subacute co-exposure induced neurotoxicity via regulating TNF-α mediated activation of NLRP3 inflammasome.

Groundwater is considered safe, however, the occurrence of contaminants like arsenic and fluoride has raised a major healthcare concern. Clinical studies suggested that arsenic and fluoride co-exposure induced neurotoxicity, however efforts to explore safe and effective management of such neurotoxicity are limited. Therefore, we investigated the ameliorative effect of Fisetin against arsenic and fluoride subacute co-exposure-induced neurotoxicity, and associated biochemical and molecular changes. Male BALB/c mice were exposed to Arsenic (NaAsO2: 50 mg/L) and fluoride (NaF: 50 mg/L) through drinking water and fisetin (5, 10, and 20 mg/kg/day) was administered orally for 28 days. The neurobehavioral changes were recorded in the open field, rotarod, grip strength, tail suspension, forced swim, and novel object recognition test. The co-exposure resulted in anxiety-like behaviour, loss of motor coordination, depression-like behaviour, and loss of novelty-based memory, along with enhanced prooxidant, inflammatory markers and loss of cortical and hippocampal neurons. The treatment with fisetin reversed the co-exposure-induced neurobehavioral deficit along with restoration of redox & inflammatory milieu, and cortical and hippocampal neuronal density. Apart from antioxidants, inhibition of TNF-α/ NLRP3 expression has been suggested as one of the plausible neuroprotective mechanisms of Fisetin in this study.