MiR-23b-3p is a promising therapeutic target for Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by memory loss, cognitive impairment and personality changes in the elderly. The main pathological features of the brain in AD patients are the presence of extracellular amyloid plaques composed of amyloid b (Ab) and intracellular neurogenic fiber tangles (NFTs) composed of hyperphosphorylated tau proteins, which ultimately lead to neuronal loss.

Despite the fact that tau proteins are known to be downstream targets of antibody-induced neurodegeneration, autopsy studies suggest that the severity of AD symptoms is more closely linked to the degree of tau-related pathology than to antibody deposition.

Aberrant microRNA (miRNA) expression in the brain can cause cognitive dysfunction and abnormal tau protein hyperphosphorylation in Alzheimer's disease (AD). Several studies have suggested that microRNA-23b-3p (miR-23b-3p) plays a role in a variety of neurological disorders, although its significance in cognitive functioning is unknown.

Researchers from the Chinese Academy of Medical Sciences and Peking Union Medical College recently published an article in Molecular Therapy: Nucleic Acids titled "miR-23b-3p rescues cognition in Alzheimer's disease by reducing tau phosphorylation and apoptosis via GSK-3b signaling pathways", which strongly supports the hypothesis that miR-23b-3p plays a neuroprotective role in AD, thus identifying miR23b-3p as a promising therapeutic target for AD.

In this study, the researchers explored the potential therapeutic effects of miR23b-3p on AD and its mechanisms. Cortical miR-23b-3p expression was reduced in amyloid precursor protein (APP)/progerin 1 (PS1) double transgenic mice (APP/PS1 mice). This reduction was confirmed in APPswe cells, SAMP8 mouse brain and plasma from AD patients. In addition, the major tau protein kinase-3b (GSK-3b) associated with tau pathology was identified as a target of miR-23b-3p.

In vivo functional studies showed that miR-23b-3p injection in the ventricles of APP/PS1 mice ameliorated cognitive deficits, histopathological alterations and tau phosphorylation immunoreactivity at multiple sites by inhibiting GSK-3b expression and activation. Similarly, upregulation of miR-23b-3p in APPswe cells inhibited GSK-3b-mediated tau hyperphosphorylation, AB1-42 production and neuronal apoptosis, leading to inhibition of GSK-3b/p-tau and Bax/caspase-3 pathways.

In conclusion, researchers' in vitro and in vivo results provide evidence that miR-23b-3p plays a protective role in AD by reducing apoptosis due to tau hyperphosphorylation. miR-23b-3p-associated neuroprotective mechanism may be that miR-23b-3p inhibits GSK-3b in the brain. miR-23b-3p is therefore a novel therapeutic potential target for therapeutic strategies for the treatment of AD.

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