Taurine Directly Binds to Oligomeric Amyloid-β and Recovers Cognitive Deficits in Alzheimer Model Mice

Abstract

Alzheimer's disease (AD) is the most common cause of dementia leading to severe cognitive decline. During the progression of AD, amyloid-β (Aβ) monomers aggregate into neurotoxic soluble oligomeric Aβ that causes cognitive impairments. Our previous study indicates that oral supplementation of taurine at 1000 mg/kg/day significantly ameliorates hippocampal-dependent cognitive deficits in APP/PS1 transgenic AD mouse model. However, Aβ plaques and oligomeric Aβ levels are not affected after administration of taurine and the oral dosage of taurine was relatively high. Thus, in this study, we focused on direct correlation between taurine and oligomeric Aβ, causing memory deficits in a lower oral dosage of taurine, 250 mg/kg/day. We induced AD-like cognitive impairments to adult normal mice and orally administered taurine via drinking water for 10 days. We confirmed that taurine administration improved cognitive deficits in oligomeric Aβ-infusion mice in Y-maze and passive avoidance tests without activity alteration of mice. In addition, we found that taurine directly bound to oligomeric Aβ in surface plasmon resonance analyses. Our results propose that taurine can ameliorate cognitive impairment by directly binding to oligomeric Aβ in oral administration of 250 mg/kg/day for 10 days.

Evaluation of the neuroprotective effect of taurine in Alzheimer’s disease using functional molecular imaging

“…Kim et al 40 reported that taurine significantly ameliorated hippocampus-related cognitive deficits in an AD mouse model. In another recent study, taurine was reported to bind directly to AβO and consequently ameliorated the behavioral deficiencies of AD, such as the loss of learning and memory 18 . Roberto et al 26 reported that taurine strongly protected neurons against the neurotoxicity of Aβ in vitro.…”

“…Soluble AβO appears to be a more toxic and disease-relevant element in AD pathogenesis than plaques 47 – 49 . Jang et al 18 reported that taurine did not affect Aβ plaque levels in the APP/PS1 model but interacted directly with AβO, which led to enhanced memory function. Lesné et al 50 reported that Aβ plaques did not induce memory impairment in the absence of AβO in Tg2576 mice.…”

“…Multiple lines of evidence suggest taurine as a therapeutic agent for AD. Recently, taurine was reported to help improve cognitive function and protect against neuropathology in an animal model of AD 18 . Jakaria et al 19 reported that taurine displayed therapeutic potential against neurological disorders, including AD.…”

Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases

“…Representing a significant hallmark of NDs, this serves dual purpose, in the early-stage diagnosis of disease as well as in developing therapeutics for them. In the case of AD, taurine supplementation exerts its therapeutic effect by reducing Aβ aggregation [202]. Kim et al demonstrated that oral administration of taurine to a APP/PS1 transgenic mouse model relieves its cognitive defects via decreasing the Aβ levels [203].…”

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer&rsquo;s Disease<strong> </strong>

“…Taurine is one of the most common free amino acids in the brain. Brain taurine levels are significantly decreased in AD, thereby preventing taurine's binding to oligomeric Aβ and its cognition-enhancing effects [169]. Taurine also attenuates Aβ42-induced mitochondrial dysfunction via SIRT1 induction [170] as well as modulating the gut microbiome and its influence on the immune system [171].…”