Study on multi-target effects of the novel HDAC6 inhibitor W5 on Aβ/Cu-induced Alzheimer's disease model of rats.

Histone deacetylase 6 (HDAC6) is a key therapeutic target in neurodegenerative diseases such as Alzheimer's disease (AD), which has been demonstrated to play an essential role in memory function and microtubule-associated tau physiology. In this study, W5 was used to treat AD model rats induced by Aβ/Cu to study the improving effect of W5 on learning and memory impairment in AD rats and its related mechanism, to provide the basis for the subsequent development of W5 as an anti-AD drug. Results showed that W5 could decrease the expression of Aβ, Tau, and p-Tau proteins in the hippocampus of AD rats to inhibit the formation of senile plaques and neurofibrillary tangles, down-regulate the expression of Bax mRNA and Caspase-3 mRNA, and up-regulate the expression of Bcl-2 mRNA to reduce the apoptosis of neuron cells, reverse the expression of TNF-α, IL-1β and IL-6 mRNA to regulate neuroinflammatory response in AD rat brain.

Rutin, Puerarin and Silymarin Regulated Aluminum-Induced Imbalance of Neurotransmitters and Metal Elements in Brain of Rats.

Non-specifically binding of aluminum to various substances in the organism can result in toxicity. The accumulation of large amounts of aluminum can cause an imbalance in metal homeostasis and interfere with the synthesis and release of neurotransmitters. Flavonoids have strong metal chelating activity, which can reduce damage to the central nervous system.

A quantitative analysis method for a new glycogen synthase kinase-3 inhibitor and its pharmacokinetics in rats.

Alzheimer's disease (AD), as a chronic and frequent neurodegenerative disease in the elderly population, has caused a huge economic burden to society, family, and other aspects. (E)-N-(4-(((2-amino-5-phenylpyridin-3-yl) imino) methyl) pyridine-2-yl) cyclopropanecarboxamide (PIMPC), a new glycogen synthase kinase-3 (GSK-3) inhibitor, has been designed and synthesized as a potential anti-AD compound with antioxidant and metal chelating properties. In this study, we established an HPLC method for the determination of PIMPC, which has high accuracy, good sensitivity, and repeatability.

Study on multi-target effects of PIMPC on Aβ/Cu-induced Alzheimer's disease model of rats.

Glycogen synthase kinase-3 (GSK-3), a key role in the pathogenesis of Alzheimer's disease (AD), has been linked with the formation of β-amyloid (Aβ), tubulin-associated unit (tau) protein phosphorylation and apoptosis. Moreover, the excessive presence of elements such as copper (Cu) can promote Aβ aggregation and increase the risk of AD. Combined with the role of GSK-3 and metal elements in AD, a metal-chelating imine GSK-3 inhibitor N-(4-{[(2-amino-5-phenylpyridin-3-ylidene)imino]methyl}pyridin-2-yl)cyclopropanecarboxamide (PIMPC) was designed and synthesized.