Guanying You

Vanadium is a well-known essential trace element, which usually exists in oxidation states in the form of a vanadate cation intracellularly. The pharmacological study of vanadium began with the discovery of its unexpected inhibitory effect on ATPase. Thereafter, its protective effects on β cells and its ability in glucose metabolism regulation were observed from the vanadium compound, leading to the application of vanadium compounds in clinical trials for curing diabetes. Alzheimer’s disease (AD) is the most common dementia disease in elderly people. However, there are still no efficient agents for treating AD safely to date. This is mainly because of the complexity of the pathology, which is characterized by senile plaques composed of the amyloid-beta (Aβ) protein in the parenchyma of the brain and the neurofibrillary tangles (NFTs), which are derived from the hyperphosphorylated tau protein in the neurocyte, along with mitochondrial damage, and eventually the central nervous system (CNS) atrophy. AD was also illustrated as type-3 diabetes because of the observations of insulin deficiency and the high level of glucose in cerebrospinal fluid (CSF), as well as the impaired insulin signaling in the brain. In this review, we summarize the advances in applicating the vanadium compound to AD treatment in experimental research and point out the limitations of the current study using vanadium compounds in AD treatment. We hope this will help future studies in this field.

Vanadium is a well-known essential trace element, which usually exists in oxidation states in form of vanadate cation intracellularly. The pharmacological study of vanadium begins at the discovery of its unexpected inhibitory effect on ATPase. Thereafter, the protective effects on cells and the abilities in glucose metabolism regulation were observed from vanadium compound, leading to the application of vanadium compounds in clinical trials for curing diabetes. Alzheimer’s dis-ease (AD) is the most common dementia disease in elderly people. However, there is still no efficient agents for treating AD safely to date. This is mainly because of the complexity of the pathology, which are characterized by the senile plaques composed by amyloid-beta (Aβ) protein in the parenchyma of brain and the neurofibrillary tangles (NFTs) derived from hyperphosphorylated tau protein in neurocyte, along with mitochondrial damage, and eventually the central nervous system (CNS) atrophy. AD was also illustrated as type-3 diabetes, because of the observations of insulin deficiency and the high level of glucose in cerebrospinal fluid (CSF), as well as the im-paired insulin signaling in brain. In this review, we summarized the advance of applicating vanadium compound on AD treatment in experimental research and pointed out the limitation of the current study on using vanadium compounds in AD treatment. We hope it will help the future study in this field.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by senile plaques formed by amyloid-beta (Aβ) extracellularly and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein intracellularly. Apart from these two features, insulin deficiency and insulin resistance have also been observed in AD brains. Thus, AD has also been referred to as type 3 diabetes by some of the scientists in this field. Insulin plays a pivotal role in learning and memory and is involved in regulating tau phosphorylation though the PI3KAkt-GSK3b signaling pathway. Interestingly, recent studies revealed that in AD brains the microglia transformed into a disease-associated microglia (DAM) status in a TREM2-dependent manner to restrain the toxicity of Aβ and propagation of tau. This also correlated with PI3K-Akt signaling through the adaptor of TREM2. Whether insulin has any effect on microglia activation in AD pathology is unclear so far. However, many studies demonstrated that diabetes increased the risk of AD. In this review, we summarize the main strategies for curing AD, including lowering the level of Aβ, suppressing the phosphorylation of tau, the ablation and/or repopulation of microglia, and especially the supply of insulin. We also propose that attention should be given to the influences of insulin on microglia in AD.

Alzheimer’s disease (AD) is an intractable neurodegenerative disease that leads to dementia, primarily in elderly people. The neurotoxicity of amyloid-beta (Aβ) and tau protein has been demonstrated over the last two decades. In line with these findings, several etiological hypotheses of AD have been proposed, including the amyloid cascade hypothesis, the oxidative stress hypothesis, the inflammatory hypothesis, the cholinergic hypothesis, et al. In the meantime, great efforts had been made in developing effective drugs for AD. However, the clinical efficacy of the drugs that were approved by the US Food and Drug Association (FDA) to date were determined only mild/moderate. We recently adopted a vanadium compound bis(ethylmaltolato)-oxidovanadium (IV) (BEOV), which was originally used for curing diabetes mellitus (DM), to treat AD in a mouse model. It was shown that BEOV effectively reduced the Aβ level, ameliorated the inflammation in brains of the AD mice, and improved the spatial learning and memory activities of the AD mice. These finding encouraged us to further examine the mechanisms underlying the therapeutic effects of BEOV in AD. In this review, we summarized the achievement of vanadium compounds in medical studies and investigated the prospect of BEOV in AD and DM treatment.

MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in Neisseria gonorrhoeae, which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3. MsrA can reduce free or protein-containing L-Met-O (S), whereas MsrBs can only function on the L-Met-O (R) epimer in proteins. Though there are isomerases existent that could transfer L-Met-O (S) to L-Met-O (R) and vice-versa, the loss of Msr individually results in different phenotypes in mice models. These observations indicate that the function of one Msr cannot be totally complemented by another. Among the mammalian Msrs, MsrB1 is the only selenocysteine-containing protein, and we recently found that loss of MsrB1 perturbs the synaptic plasticity in mice, along with the astrogliosis in their brains. In this review, we summarized the effects resulting from Msr deficiency and the bioactivity of selenium in the central nervous system, especially those that we learned from the MsrB1 knockout mouse model. We hope it will be helpful in better understanding how the trace element selenium participates in the reduction of L-Met-O and becomes involved in neurobiology.