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Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer’s disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that oxidative stress induced by beta-amyloid (Aβ) is implicated in the pathlogical progression of Alzheimer’s disease (AD). 3H-1,2-dithiole-3-thione (D3T), the simplest compound of the sulfur-containing dithiolethiones, has been proved to be a strongly active antioxidant factor by regulation of the nuclear factor E2-related factor 2 (Nrf2). Previous study reported that D3T confers protection to AD cell model in vitro, however, the neuroprotective effect of D3T in the AD mammalian model is unknown. In the present study, we aimed to evaluate the therapeutic potential of D3T in the Tg2576 AD mouse model and investigate the mechanisms underlying its beneficial effects. We showed that intraperitoneal administration of D3T significantly alleviated cognitive deficits in AD mice and dramatically decreased insoluble Aβ level and oxidative stress. Further mechanistic studies revealed that D3T significantly promoted hippocampal neurogenesis, and up-regulated levels of silent information regulator 1 (Sirt1), Nrf2 and heme oxygenase-1 (HO-1). Moreover, the positive effect of D3T on behavioral performance of AD mice was markedly attenuated by inhibition of the Sirt1/Nrf2 pathway by the antagonist EX527. In summary, our studies on a mouse AD model indicate that D3T could serve as a potential therapeutic agent for this devastating disease. [ABSTRACT FROM AUTHOR]

Stem cell transplantation represents a promising therapy for central nervous system injuries, but its application to Alzheimer’s disease (AD) is still limited and the potential mechanism for cognition improvement remains to be elucidated. In the present study, we used Tg2576 mice which express AD-like pathological forms of amyloid precursor protein (APP) to investigate the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) intravenous transplantation on AD mice. Interestingly, hUC-MSCs transplantation significantly ameliorated cognitive function of AD mice without altering Aβ levels in hippocampus. Remarkably, hUC-MSCs transplantation reduced oxidative stress in hippocampus of AD mice by decreasing the level of malondialdehyde (MDA), increasing the level of nitric oxide (NO), enhancing the activity of superoxide dismutase (SOD) and neuronal nitric oxide synthase (nNOS). The mechanisms underlying the improved cognitive function may be linked to hippocampal neurogenesis and an up-regulation of neuronal synaptic plasticity related proteins levels including silent information regulator 1 (Sirt1), brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN). Taken together, our findings suggest that hUC-MSCs can improve cognition of AD mice by decreasing oxidative stress and promoting hippocampal neurogenesis. These results suggest that modulating hUC-MSCs to generate excess neuroprotective factors could provide a viable therapy to treat AD. [ABSTRACT FROM AUTHOR]