Nanoconjugate Improves Cognitive Deficit and Limits the Pathogenic Tau Burden in Okadaic-Acid-Induced Alzheimer's Mice

Alzheimer's disease (AD) is characterized by a progressive loss of cognition and its distinct hyperphosphorylated Tau (p-tau) pathology. Both insulin resistance(IRT) and p-tau share a causal relationship in AD, whereas the connective mechanism between them remains largely unknown. Tau protein is considered the primary target to combat AD as loss of Tau function triggers neuronal loss in AD. In the prior report, it is observed that self-therapeutic gold nanoparticles alleviate Tauopathy in models of AD. Gold nanoparticles (AuNPs)& horbar;polyethylene glycol 2000 (PEG(2000))& horbar;transferrin (Tf) nanoconjugate is synthesized for passive targeting to pharmacologically regulate neuronal tau. It is observed that AuNPs & horbar;PEG(2000)& horbar;Tf decreases p-tau while restores insulin receptor(IR) and activates protein kinase B (AKT) kinase in SHSY5Y cell overexpressing Tau. AuNPs & horbar;PEG(2000)& horbar;Tf downregulates transferrin receptor by inhibiting recombinant divalent metal transporter 1 protein, affecting Fe2+ accumulation. AuNPs & horbar;PEG(2000)& horbar;Tf improves learning ability of mice in okadaic-acid-induced, stereotaxic model in a dose-dependent fashion compared to memantine and subsequently decreases both p-tau and acetyl tau levels and upregulates the AKT signal. Changes in p-tau/Tau index from mouse brain homogenate is diminished following AuNPs & horbar;PEG(2000)& horbar;Tf treatment as a desired therapeutic outcome. Given AuNPs & horbar;PEG(2000)& horbar;Tf treatment restricts pathogenic conversion of Tau (p-tau, acetyl Tau), further investigation is warranted to bridge the connection between gold-nanoparticle-mediated alteration of IRT and AD progression.