Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer’s Disease

Zhou, Xun; Wu, Xiaolang; Wang, Rui; Han, Lu; Li, Huilin; Zhao, Wei

doi:10.3390/ijms25010170

Cited by 4 publications

(1 citation statement)

References 135 publications

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“…The limited expression of HMGCR and DHCR24 and lower cholesterol content in our Ts2 mouse model and ApoE4 astrocytes [29] imply meaningful issues about the pharmacological treatment of AD-like neurodegeneration with the use of lipid lowering agents, in particular statins which are HMGCR inhibitors. Although the effects of statins are mainly at the systemic level, these drugs, in particular the lipophilic simvastatin which appears the most effective at crossing the BBB, are proposed as neuroprotective in the early stages of AD thanks to their hypocholesterolemic activity, and antioxidant and anti-inflammatory properties [49][50][51]. Statins can indeed inhibit neuroinflammation and associated neurodegenerative complications through inhibition of microglia and astrocyte activation, and of the release of pro-inflammatory cytokines [52,53].…”

Section: Discussionmentioning

confidence: 99%

Altered Brain Cholesterol Machinery in a Down Syndrome Mouse Model: A Possible Common Feature with Alzheimer’s Disease

Staurenghi,

Testa,

Leoni

et al. 2024

Antioxidants

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Down syndrome (DS) is a complex chromosomal disorder considered as a genetically determined form of Alzheimer’s disease (AD). Maintenance of brain cholesterol homeostasis is essential for brain functioning and development, and its dysregulation is associated with AD neuroinflammation and oxidative damage. Brain cholesterol imbalances also likely occur in DS, concurring with the precocious AD-like neurodegeneration. In this pilot study, we analyzed, in the brain of the Ts2Cje (Ts2) mouse model of DS, the expression of genes encoding key enzymes involved in cholesterol metabolism and of the levels of cholesterol and its main precursors and products of its metabolism (i.e., oxysterols). The results showed, in Ts2 mice compared to euploid mice, the downregulation of the transcription of the genes encoding the enzymes 3-hydroxy-3-methylglutaryl-CoA reductase and 24-dehydrocholesterol reductase, the latter originally recognized as an indicator of AD, and the consequent reduction in total cholesterol levels. Moreover, the expression of genes encoding enzymes responsible for brain cholesterol oxidation and the amounts of the resulting oxysterols were modified in Ts2 mouse brains, and the levels of cholesterol autoxidation products were increased, suggesting an exacerbation of cerebral oxidative stress. We also observed an enhanced inflammatory response in Ts2 mice, underlined by the upregulation of the transcription of the genes encoding for α-interferon and interleukin-6, two cytokines whose synthesis is increased in the brains of AD patients. Overall, these results suggest that DS and AD brains share cholesterol cycle derangements and altered oxysterol levels, which may contribute to the oxidative and inflammatory events involved in both diseases.

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Section: Discussionmentioning

confidence: 99%

Altered Brain Cholesterol Machinery in a Down Syndrome Mouse Model: A Possible Common Feature with Alzheimer’s Disease

Staurenghi,

Testa,

Leoni

et al. 2024

Antioxidants

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Statins as Neuroinflammatory Therapy, Bibliometric Study

SALEH,

Susanto,

Valentina

et al. 2024

F1000Res

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Introduction Neuroinflammase, a key mechanism in neurodegenerative diseases like Alzheimer and Parkinson, is influenced by statin, a lipid-binding protein. Studies show that statin can mitigate the likelihood of developing dementia and Alzheimer’s disease and can also reduce leukocytosis and T-regulatory function. Nevertheless, there is restricted literature on the use of statin in neuroinflammation. The objective of this investigation is to conduct a bibliometric analysis of statin use in neuroinflammation, providing valuable insights into research development and future research questions. Methods In this work, a literature review methodology is employed to gather data from the Scopus database using the keywords neuroinflammation and statins. Data were analyzed using Biblioshiny and VOSviewer software to produce visualizations and bibliometric maps. We conducted quantitative and qualitative analysis. Results The research trend found are Documents by Year, Most Global Cited Document, Most Relevant Sources, Factorial Map Of The Documents With The Highest Contributes, Documents by Author, Most Relevant Affiliations, Documents by Subject Area, Trend Topic, Network Visualization, Overlay visualization of scopus, database using Vosviewer, Density Visualization, Thematic Map, Thematic Evolution, Cluster Analysis, Qualitative Analysis, and Word Cloud. Conclusions The study highlights the potential for further research on statins and neuroinflammation, aiming to better understand their role in treating neuroinflammation and enhance the quality of life for patients with neuroinflammatory conditions.

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Association Between Statin Use and Dementia, and Related Mechanisms: A Bibliometric Analysis from 2007 to 2023

Sang,

Chen,

Hou

et al. 2024

JAD

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Background: Emerging evidence suggests the potential of hydroxymethylglutaryl-coenzyme A (HMG-CoA, statins) as a therapeutic option for dementia. Objective: The primary objective of this study is to assess the current state of research on statins use in dementia, with a focus on identifying pivotal questions within the field. Methods: A systemic search for publications on statin use in dementia between 2007 and 2023 was conducted, utilizing the Web of Science Core Collection. The scientific output was analyzed from various perspectives through VOSviewer, CiteSpace, and the bibliometrics website (https://bibliometric.com/). Results: 560 articles authored by 2,977 individuals and 999 institutions across 58 countries were included, which were published in 295 periodicals and cited 21,176 references from 16,424 authors. The annual publication output remained steady, while the number of citations increased consistently. The U.S. and Mayo Clinic emerged as the most significant country and institution, respectively. B. McGuinness and D.L. Sparks were the most eminent authors. Journal of Alzheimer’s Disease was the most influential journal. Three sets of keywords and the top 10 references were identified, suggesting pivotal questions within the field. Conclusions: While statins show promising potential as a treatment option for dementia, their use remains uncertain due to the reported short-term cognitive impairment events and questionable long-term protective effects against dementia. The pivotal question is to ascertain the association between statins and cognition. The mechanisms underlying the effects of statins on cognition are multifaceted. This study provides insights into the current status within the field of statin use in dementia.

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Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer’s Disease

Cited by 4 publications

References 135 publications

Altered Brain Cholesterol Machinery in a Down Syndrome Mouse Model: A Possible Common Feature with Alzheimer’s Disease

Altered Brain Cholesterol Machinery in a Down Syndrome Mouse Model: A Possible Common Feature with Alzheimer’s Disease

Statins as Neuroinflammatory Therapy, Bibliometric Study

Association Between Statin Use and Dementia, and Related Mechanisms: A Bibliometric Analysis from 2007 to 2023

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