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Statin effects on cholesterol micro-domains in brain plasma membranes
Kirsch C, Eckert GP, Mueller WE.. Biochemical pharmacology, 2003-03-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
Recent epidemiological studies revealed inhibitors of the hydroxymethylglutaryl-coenzyme A reductase, so-called statins, to be effective in lowering the prevalence of Alzheimer's disease (AD). In vitro, statins strongly reduced the cellular amyloid beta-protein load by modulating the processing of the amyloid beta precursor protein. Both observations are probably linked to cellular cholesterol homeostasis in brain. So far, little is known about brain effects of statins. Recently, we could demonstrate that treatment of mice with the lipophilic compound lovastatin resulted in a discrete reduction of brain membrane cholesterol levels. To follow up these findings, we subsequently carried out a further in vivo study including lovastatin and simvastatin as lipophilic agents, as well as pravastatin as a hydrophilic compound, focussing on their efficiency to affect subcellular membrane cholesterol pools in synaptosomal plasma membranes of mice. In contrast to the hydrophilic pravastatin, the lipophilic lovastatin and simvastatin strongly reduced the levels of free cholesterol in SPM. Interestingly, lovastatin and pravastatin but not simvastatin significantly reduced cholesterol levels in the exofacial membrane leaflet. These changes were accompanied by modified membrane bulk fluidity. All three statins reduced the expression of the raft marker protein flotillin. Alterations in transbilayer cholesterol distribution have been suggested as the underlying mechanism that forces amyloidogenic processing of APP in AD. Thus, our data give some first insight in the mode of action of statins to reduce the prevalence of AD in clinical trials.
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APA 7th
Kirsch, C., Eckert, G. P., & Mueller, W. E. (2003). Statin effects on cholesterol micro-domains in brain plasma membranes. Biochemical pharmacology. https://doi.org/10.1016/s0006-2952(02)01654-4
Vancouver
Kirsch C, Eckert GP, Mueller WE. Statin effects on cholesterol micro-domains in brain plasma membranes. Biochemical pharmacology. 2003. doi:10.1016/s0006-2952(02)01654-4. PMID: 12628479.
BibTeX
@article{kirsch2003-12628479,
author = {Kirsch, C. and Eckert, G. P. and Mueller, W. E.},
title = {{Statin effects on cholesterol micro-domains in brain plasma membranes}},
journal = {Biochemical pharmacology},
year = {2003},
doi = {10.1016/s0006-2952(02)01654-4},
pmid = {12628479},
url = {https://doi.org/10.1016/s0006-2952(02)01654-4}
}
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Key findings
- Recent epidemiological studies revealed inhibitors of the hydroxymethylglutaryl-coenzyme A reductase, so-called statins, to be effective in lowering the prevalence of Alzheimer's disease (AD).
- To follow up these findings, we subsequently carried out a further in vivo study including lovastatin and simvastatin as lipophilic agents, as well as pravastatin as a hydrophilic compound, focussing on their efficiency to affect subcellular membrane cholesterol pools in synaptosomal plasma membranes of mice.
- Interestingly, lovastatin and pravastatin but not simvastatin significantly reduced cholesterol levels in the exofacial membrane leaflet.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biochemical pharmacology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2003 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12628479) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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