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Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death
Martin LJ, Pan Y, Price AC, Sterling W, Copeland NG, Jenkins NA, Price DL, Lee MK.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006-01-01
Topic: Brain proteins, microglia and lab models
Alpha-synuclein (alpha-Syn) is enriched in nerve terminals. Two mutations in the alpha-Syn gene (Ala53--> Thr and Ala30--> Pro) occur in autosomal dominant familial Parkinson's disease. Mice overexpressing the human A53T mutant alpha-Syn develop a severe movement disorder, paralysis, and synucleinopathy, but the mechanisms are not understood. We examined whether transgenic mice expressing human wild-type or familial Parkinson's disease-linked A53T or A30P mutant alpha-syn develop neuronal degeneration and cell death. Mutant mice were examined at early- to mid-stage disease and at near end-stage disease. Age-matched nontransgenic littermates were controls. In A53T mice, neurons in brainstem and spinal cord exhibited large axonal swellings, somal chromatolytic changes, and nuclear condensation. Spheroid eosinophilic Lewy body-like inclusions were present in the cytoplasm of cortical neurons and spinal motor neurons. These inclusions contained human alpha-syn and nitrated synuclein. Motor neurons were depleted (approximately 75%) in A53T mice but were affected less in A30P mice. Axonal degeneration was present in many regions. Electron microscopy confirmed the cell and axonal degeneration and revealed cytoplasmic inclusions in dendrites and axons. Some inclusions were degenerating mitochondria and were positive for humanalpha-syn. Mitochondrial complex IV and V proteins were at control levels, but complex IV activity was reduced significantly in spinal cord. Subsets of neurons in neocortex, brainstem, and spinal cord ventral horn were positive for terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, cleaved caspase-3, and p53. Mitochondria in neurons had terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive matrices and p53 at the outer membrane. Thus, A53T mutant mice develop intraneuronal inclusions, mitochondrial DNA damage and degeneration, and apoptotic-like death of neocortical, brainstem, and motor neurons.
Key findings
- Electron microscopy confirmed the cell and axonal degeneration and revealed cytoplasmic inclusions in dendrites and axons.
- Mitochondrial complex IV and V proteins were at control levels, but complex IV activity was reduced significantly in spinal cord.
Why it matters
In this mouse study, animals making mutant human alpha-synuclein developed nerve cell damage and death along with reduced activity of mitochondrial complex IV in the spinal cord. These findings come from genetically modified mice, not people, so they do not yet show how Parkinson's disease should be treated in patients.
Study details
- Evidence strengthLow
How this study scored 53/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | 4 / 4 | Journal of Neuroscience: journal h-index 651 (OpenAlex, 2026-10-29) |
| 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 | 2006 — 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 | Laboratory or animal study (title names “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 682 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 31.0 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 5 / 6 | Cited 24.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 3 / 4 | Cited 51 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Michael K. Lee: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16399671) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1523/jneurosci.4308-05.2006
- PubMed: 16399671
- Original source →
- Free full text: Journal of Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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 8 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.
APA 7th
Martin, L. J., Pan, Y., Price, A. C., Sterling, W., Copeland, N. G., Jenkins, N. A., et al. (2006). Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.4308-05.2006
Vancouver
Martin LJ, Pan Y, Price AC, Sterling W, Copeland NG, Jenkins NA, et al. Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006. doi:10.1523/jneurosci.4308-05.2006. PMID: 16399671.
BibTeX
@article{martin2006-16399671,
author = {Martin, L. J. and Pan, Y. and Price, A. C. and Sterling, W. and Copeland, N. G. and Jenkins, N. A. and Price, D. L. and Lee, M. K.},
title = {{Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2006},
doi = {10.1523/jneurosci.4308-05.2006},
pmid = {16399671},
url = {https://doi.org/10.1523/jneurosci.4308-05.2006}
}
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