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Real-time imaging of mitochondrial redox reveals increased mitochondrial oxidative stress associated with amyloid β aggregates in vivo in a mouse model of Alzheimer's disease
Calvo-Rodriguez M, Kharitonova EK, Snyder AC, Hou SS, Sanchez-Mico MV, Das S, Fan Z, Shirani H et al.. Molecular neurodegeneration, 2024-01-18
Topic: Disease mechanisms in lab and animal studies
Background Reactive oxidative stress is a critical player in the amyloid beta (Aβ) toxicity that contributes to neurodegeneration in Alzheimer's disease (AD). Damaged mitochondria are one of the main sources of reactive oxygen species and accumulate in Aβ plaque-associated dystrophic neurites in the AD brain. Although Aβ causes neuronal mitochondria reactive oxidative stress in vitro, this has never been directly observed in vivo in the living mouse brain. Here, we tested for the first time whether Aβ plaques and soluble Aβ oligomers induce mitochondrial oxidative stress in surrounding neurons in vivo, and whether this neurotoxic effect can be abrogated using mitochondrial-targeted antioxidants. Methods We expressed a genetically encoded fluorescent ratiometric mitochondria-targeted reporter of oxidative stress in mouse models of the disease and performed intravital multiphoton microscopy of neuronal mitochondria and Aβ plaques. Results For the first time, we demonstrated by direct observation in the living mouse brain exacerbated mitochondrial oxidative stress in neurons after both Aβ plaque deposition and direct application of soluble oligomeric Aβ onto the brain, and determined the most likely pathological sequence of events leading to oxidative stress in vivo. Oxidative stress could be inhibited by both blocking calcium influx into mitochondria and treating with the mitochondria-targeted antioxidant SS31. Remarkably, the latter ameliorated plaque-associated dystrophic neurites without impacting Aβ plaque burden. Conclusions Considering these results, combination of mitochondria-targeted compounds with other anti-amyloid beta or anti-tau therapies hold promise as neuroprotective drugs for the prevention and/or treatment of AD.
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APA 7th
Calvo-Rodriguez, M., Kharitonova, E. K., Snyder, A. C., Hou, S. S., Sanchez-Mico, M. V., Das, S., et al. (2024). Real-time imaging of mitochondrial redox reveals increased mitochondrial oxidative stress associated with amyloid β aggregates in vivo in a mouse model of Alzheimer's disease. Molecular neurodegeneration. https://doi.org/10.1186/s13024-024-00702-2
Vancouver
Calvo-Rodriguez M, Kharitonova EK, Snyder AC, Hou SS, Sanchez-Mico MV, Das S, et al. Real-time imaging of mitochondrial redox reveals increased mitochondrial oxidative stress associated with amyloid β aggregates in vivo in a mouse model of Alzheimer's disease. Molecular neurodegeneration. 2024. doi:10.1186/s13024-024-00702-2. PMID: 38238819.
BibTeX
@article{calvorodriguez2024-38238819,
author = {Calvo-Rodriguez, M. and Kharitonova, E. K. and Snyder, A. C. and Hou, S. S. and Sanchez-Mico, M. V. and Das, S. and Fan, Z. and Shirani, H. and others},
title = {{Real-time imaging of mitochondrial redox reveals increased mitochondrial oxidative stress associated with amyloid β aggregates in vivo in a mouse model of Alzheimer's disease}},
journal = {Molecular neurodegeneration},
year = {2024},
doi = {10.1186/s13024-024-00702-2},
pmid = {38238819},
url = {https://doi.org/10.1186/s13024-024-00702-2}
}
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Key findings
- Results For the first time, we demonstrated by direct observation in the living mouse brain exacerbated mitochondrial oxidative stress in neurons after both Aβ plaque deposition and direct application of soluble oligomeric Aβ onto the brain, and determined the most likely pathological sequence of events leading to oxidative stress in vivo.
- Conclusions Considering these results, combination of mitochondria-targeted compounds with other anti-amyloid beta or anti-tau therapies hold promise as neuroprotective drugs for the prevention and/or treatment of AD.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported 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 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular neurodegeneration) |
| 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 | 4 / 5 | 2024 — within 3 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 | Laboratory or animal study (title names “mouse”) — scores zero |
| 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 38238819) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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