Lipid-core nanocapsules containing simvastatin improve the cognitive impairment induced by obesity and hypercholesterolemia in adult rats

Lorenzoni, Ricardo; Davies, Samuel; Cordenonsi, Leticia Malgarim; Viçosa, José Alcides da Silva; Mezzomo, Nathana J.; Oliveira, Amanda Lima de; Carmo, Guilherme M. do; Raffin, Renata Platcheck; Alves, Oswaldo Luiz; Vaucher, Rodrigo de Almeida; Rech, Virgínia Cielo

doi:10.1016/j.ejps.2020.105397

Cited by 11 publications

(6 citation statements)

References 83 publications

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Section: Discussionmentioning

confidence: 99%

“…Interesting, many drugs were involved in our drug-gene-interaction network. Inspiring, some of them were undergoing the examination its effect on AD, such as statins (simvastatin, 47,48 lovastatin, 49 and aspirin 50,51 ). Although these studies have not yet obtained conformance evaluation of AD in human populations, the results in Figure 6 indicate that more drugs may be available for the treatment of AD in the future.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of Serum miRNAs in Alzheimer’s Disease

Lü

Dai

Zhu

et al. 2021

Am J Alzheimers Dis Other Demen

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This paper was aimed to analyze the microRNA (miRNA) signatures in Alzheimer disease (AD) and find the significant expressions of miRNAs, their target genes, the functional enrichment analysis of the confirmed genes, and potential drug treatment. The miRNA expression information of the gene expression profile data was downloaded from the Gene Expression Omnibus database. The total data sample size is 1309, including 1021 AD samples and 288 normal samples. A total of 21 differentially expressed miRNAs were obtained, of which 16 (hsa-miR-6761-3p, hsa-miR-6747-3p, hsa-miR-6875-3p, hsa-miR-6754-3p, hsa-miR-6736-3p, hsa-miR-6762-3p, hsa-miR-6787-3p, hsa-miR-208a-5p, hsa-miR-6740-3p, hsa-miR-6778-3p, hsa-miR-595, hsa-miR-6753-3p, hsa-miR-4747-3p, hsa-miR-3646, hsa-miR-6716-3p and hsa-miR-4435) were up-regulated and 5 (hsa-miR-125a-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-6131 and hsa-miR-125b-1-3p) were down-regulated in AD. A total of 6 miRNAs (hsa-miR-595, hsa-miR-3646, hsa-miR-4435 hsa-miR-125a-3p, hsa-miR-22-3p and hsa-miR-24-3p) and 78 miRNA-disease-related gene sub-networks were predicted, and 116 ceRNA regulatory relationship pairs, and the ceRNA regulatory network were obtained. The results of enrichment analysis suggested that the main target pathways of several miRNAs differentially expressed in AD were mitogen-activated protein kinase signal pathway. According to the prediction results of Drug-Gene Interaction database 2.0, we obtained 53 pairs of drug-gene interaction, including 7 genes (PTGS2, EGFR, CALM1, PDE4D, FGFR2, HMGCR, cdk6) and 53 drugs. We hope our results are helpful to find a viable way to prevent, delay the onset, diagnose, and treat AD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Analysis of Serum miRNAs in Alzheimer’s Disease

Lü

Dai

Zhu

et al. 2021

Am J Alzheimers Dis Other Demen

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“…ApoJ can bind Aβ, thus promoting Aβ clearance through BBB and reducing Aβ uptake ( Zandl-Lang et al, 2018 ). Although simvastatin readily passes through the BBB, a study suggests that free simvastatin failed to improve cognitive impairment caused by high-cholesterol diets and that it improves cognitive dysfunction only when simvastatin was reproduced in lipid-core nanocapsules ( Lorenzoni et al, 2020 ). However, not all studies specify that statins can protect against cognitive deficits caused by hypercholesterolemia.…”

Section: Can Cholesterol Regulation Prevent or Delay Ad?mentioning

confidence: 99%

Connecting the Dots Between Hypercholesterolemia and Alzheimer’s Disease: A Potential Mechanism Based on 27-Hydroxycholesterol

Zhai

Liang

et al. 2022

Front. Neurosci.

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Alzheimer’s disease (AD), the most common cause of dementia, is a complex and multifactorial disease involving genetic and environmental factors, with hypercholesterolemia considered as one of the risk factors. Numerous epidemiological studies have reported a positive association between AD and serum cholesterol levels, and experimental studies also provide evidence that elevated cholesterol levels accelerate AD pathology. However, the underlying mechanism of hypercholesterolemia accelerating AD pathogenesis is not clear. Here, we review the metabolism of cholesterol in the brain and focus on the role of oxysterols, aiming to reveal the link between hypercholesterolemia and AD. 27-hydroxycholesterol (27-OHC) is the major peripheral oxysterol that flows into the brain, and it affects β-amyloid (Aβ) production and elimination as well as influencing other pathogenic mechanisms of AD. Although the potential link between hypercholesterolemia and AD is well established, cholesterol-lowering drugs show mixed results in improving cognitive function. Nevertheless, drugs that target cholesterol exocytosis and conversion show benefits in improving AD pathology. Herbs and natural compounds with cholesterol-lowering properties also have a potential role in ameliorating cognition. Collectively, hypercholesterolemia is a causative risk factor for AD, and 27-OHC is likely a potential mechanism for hypercholesterolemia to promote AD pathology. Drugs that regulate cholesterol metabolism are probably beneficial for AD, but more research is needed to unravel the mechanisms involved in 27-OHC, which may lead to new therapeutic strategies for AD.

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“…At the same time, hyperlipidemia may lead to atherosclerosis in cerebrovascular arteries, and lipid accumulation affected the hippocampus such that an inflammatory response was produced [22,98]. One study found that Simvastatin improved cognitive function in mice with diabetes; nevertheless, the beneficial effects of statin therapy in patients with CI have not been firmly established [99,100]. It reported that rFGF21 treatment significantly reduced elevations in serum total cholesterol and LDL/HDL ratio, it was also confirmed to have a potent and beneficial effect in modulating hyperlipidemia in obese mice fed a high-fat diet [96].…”

Section: Dyslipidemiamentioning

confidence: 99%