Ebselen Interferes with Alzheimer’s Disease by Regulating Mitochondrial Function

Abstract

(1) Background: With unknown causes and no effective treatment available, Alzheimer’s disease (AD) places enormous pressure on families and society. Our previous study had shown that Ebselen at a high concentration (10.94 μM) improved the cognition of triple-transgenic AD (3×Tg-AD) mice and alleviated the related pathological indicators but showed toxicity to the mice. Here, we dedicated to study the therapeutic effect and molecular mechanism of Ebselen at a much lower concentration on 3×Tg-AD mice. (2) Methods: Various behavioral experiments were applied to detect the behavioral ability of mice. Western blot, thioflavin T staining and a transmission electron microscope were used to evaluate the pathology of AD mice. The mitochondrial membrane potential and respiration were assessed with the corresponding assay kit. (3) Results: Ebselen remarkably increased cognitive ability of AD mice, eliminated β-Amyloid (Aβ) oligomers and recovered the synaptic damage in AD mice brain. In addition, the destroyed mitochondrial morphologies and function were repaired by Ebselen through ameliorating mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial fusion/fission balance in N2a-SW cells and brain tissues of AD mice. (4) Conclusions: This research indicated that Ebselen might exert its therapeutic effect via protecting mitochondria in AD.

Se-methylselenocysteine ameliorates mitochondrial function by targeting both mitophagy and autophagy in the mouse model of Alzheimer's disease

“…56 However, multiple studies have demonstrated that selenium can protect mitochondrial function by upregulating mitochondrial biogenesis. 46,57–60 In the present research, after SMC treatment, AKT was activated and the levels of Nrf1, Nrf2 and mtTFA in AD models were increased (Fig. 3).…”

Neurogranin expression regulates mitochondrial function and redox balance in endothelial cells

“…MitoEbselen demonstrates potent antioxidant activity and has been observed to preserve cell function during oxidative stress in many cell types and disease models, including cardiovascular disease [ 41 ]. Furthermore, H 2 O 2 scavenging by MitoEbselen has been seen to positively influence OCR and mitochondrial function in multiple cell types, including endothelial cells [ 42 , 43 ].…”

“…Chronic, sustained increases in H 2 O 2 can negatively impact mitochondrial functioning and OCR. Therefore, H 2 O 2 scavenging by MitoEbselen has been seen to positively influence OCR and mitochondrial function in multiple cell types, including endothelial cells [ 42 , 43 ]. Notably, MitoEbselen treatment does not further increase OCR in Ng overexpression HAECs, which hints that a different pathway may become dominant in endothelial cells when Ng is overexpressed.…”

Thioredoxin-1 Promotes Mitochondrial Biogenesis Through Regulating AMPK/Sirt1/PGC1α Pathway in Alzheimer's Disease

“…Accumulating evidence have demonstrated that amelioration of mitochondrial homeostasis to restore the normal function of mitochondria is beneficial for the prevention or treatment of AD (Li et al 2022c ; Li et al, 2022b ). Thus, whether Trx-1 regulates mitochondrial homeostasis in AD was further investigated.…”