A Comparative Study between Hydrogen Peroxide Amperometric Biosensors Based on Different Peroxidases Wired by Os-Polymer: Applications in Water, Milk and Human Urine

In the last few years, hydrogen peroxide [...

A Comparative Study between Hydrogen Peroxide Amperometric Biosensors Based on Different Peroxidases Wired by Os-Polymer: Applications in Water, Milk and Human Urine

In the last few years, hydrogen peroxide [...

Benfotiamine Treatment Activates Nrf2/ARE Pathway and is Neuroprotective in a Transgenic Mouse Model of Tauopathy

peer reviewedImpaired glucose metabolism, decreased levels of thiamine (vitamin B1) and its phosphate esters, and downregulated activity of thiamine-dependent enzymes, such as pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase have been linked to Alzheimer’s disease (AD). Thiamine-deficient mice exhibit increased amyloid deposition, tau hyperphosphorylation, and oxidative damage1. Experimental evidence has shown that benfotiamine (BFT), a synthetic S-acyl derivative of thiamine, rescued cognitive deficits and reduced amyloid burden in APP/PS1 mice2. We investigated whether BFT confers neuroprotection against tau phosphorylation and the generation of neurofibrillary tangles (NFTs) ‒ which causes frontotemporal dementia in humans ‒ in a mouse model of tauopathy. Exposure to BFT resulted in increased lifespan, behavioral improvement, reduced and glycated tau and NFTs, and prevented neuronal death in P301S transgenic (TG) mice. In addition, BFT administration significantly ameliorated mitochondrial dysfunction, attenuated oxidative damage, and decreased the expression of several pro-inflammatory mediators, consistent with a possible activation of the Nrf2/ARE neuroprotective pathway. Accordingly, we found that BFT (but not thiamine) triggers the expression of Nrf2/ARE-dependent genes in wild-type (WT) but not in Nrf2-deficient fibroblasts. Our findings suggest that BFT is a promising therapeutic agent for the treatment of tauopathies