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Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease
Sheng B, Wang X, Su B, Lee HG, Casadesus G, Perry G, Zhu X.. Journal of neurochemistry, 2011-12-08
Topic: Amyloid, tau and blood-test diagnosis
Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) brain. Our prior studies demonstrated reduced mitochondrial number in susceptible hippocampal neurons in the brain from AD patients and in M17 cells over-expressing familial AD-causing amyloid precursor protein (APP) mutant (APPswe). In the current study, we investigated whether alterations in mitochondrial biogenesis contribute to mitochondrial abnormalities in AD. Mitochondrial biogenesis is regulated by the peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α)-nuclear respiratory factor (NRF)-mitochondrial transcription factor A pathway. Expression levels of PGC-1α, NRF 1, NRF 2, and mitochondrial transcription factor A were significantly decreased in both AD hippocampal tissues and APPswe M17 cells, suggesting a reduced mitochondrial biogenesis. Indeed, APPswe M17 cells demonstrated decreased mitochondrial DNA/nuclear DNA ratio, correlated with reduced ATP content, and decreased cytochrome C oxidase activity. Importantly, over-expression of PGC-1α could completely rescue while knockdown of PGC-1α could exacerbate impaired mitochondrial biogenesis and mitochondrial deficits in APPswe M17 cells, suggesting reduced mitochondrial biogenesis is likely involved in APPswe-induced mitochondrial deficits. We further demonstrated that reduced expression of p-CREB and PGC-1α in APPswe M17 cells could be rescued by cAMP in a dose-dependent manner, which could be inhibited by PKA inhibitor H89, suggesting that the PKA/CREB pathway plays a critical role in the regulation of PGC-1α expression in APPswe M17 cells. Overall, this study demonstrated that impaired mitochondrial biogenesis likely contributes to mitochondrial dysfunction in AD.
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APA 7th
Sheng, B., Wang, X., Su, B., Lee, H. G., Casadesus, G., Perry, G., et al. (2012). Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease. Journal of neurochemistry. https://doi.org/10.1111/j.1471-4159.2011.07581.x
Vancouver
Sheng B, Wang X, Su B, Lee HG, Casadesus G, Perry G, et al. Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease. Journal of neurochemistry. 2012. doi:10.1111/j.1471-4159.2011.07581.x. PMID: 22077634.
BibTeX
@article{sheng2012-22077634,
author = {Sheng, B. and Wang, X. and Su, B. and Lee, H. G. and Casadesus, G. and Perry, G. and Zhu, X.},
title = {{Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease}},
journal = {Journal of neurochemistry},
year = {2012},
doi = {10.1111/j.1471-4159.2011.07581.x},
pmid = {22077634},
url = {https://doi.org/10.1111/j.1471-4159.2011.07581.x}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Our prior studies demonstrated reduced mitochondrial number in susceptible hippocampal neurons in the brain from AD patients and in M17 cells over-expressing familial AD-causing amyloid precursor protein (APP) mutant (APPswe).
- Expression levels of PGC-1α, NRF 1, NRF 2, and mitochondrial transcription factor A were significantly decreased in both AD hippocampal tissues and APPswe M17 cells, suggesting a reduced mitochondrial biogenesis.
- Indeed, APPswe M17 cells demonstrated decreased mitochondrial DNA/nuclear DNA ratio, correlated with reduced ATP content, and decreased cytochrome C oxidase activity.
- We further demonstrated that reduced expression of p-CREB and PGC-1α in APPswe M17 cells could be rescued by cAMP in a dose-dependent manner, which could be inhibited by PKA inhibitor H89, suggesting that the PKA/CREB pathway plays a critical role in the regulation of PGC-1α expression in APPswe M17 cells.
- Overall, this study demonstrated that impaired mitochondrial biogenesis likely contributes to mitochondrial dysfunction in AD.
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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 randomised / 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 multi-centre 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 (Journal of neurochemistry) |
| 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 | 2012 — within 20 year(s) of the newest study here |
| 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) |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22077634) |
| 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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