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Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy
Crews L, Spencer B, Desplats P, Patrick C, Paulino A, Rockenstein E, Hansen L, Adame A et al.. PloS one, 2010-02-19
This paper has been retracted. The record we hold marks it as a retracted publication. Check the original source below for the retraction notice before relying on anything it reports.
Topic: Brain proteins, microglia and lab models
Background Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by alpha-synuclein accumulation that includes dementia with Lewy bodies (DLB) and Parkinson's Disease (PD). Recent evidence suggests that impairment of lysosomal pathways (i.e. autophagy) involved in alpha-synuclein clearance might play an important role. For this reason, we sought to examine the expression levels of members of the autophagy pathway in brains of patients with DLB and Alzheimer's Disease (AD) and in alpha-synuclein transgenic mice. Methodology/principal findings By immunoblot analysis, compared to controls and AD, in DLB cases levels of mTor were elevated and Atg7 were reduced. Levels of other components of the autophagy pathway such as Atg5, Atg10, Atg12 and Beclin-1 were not different in DLB compared to controls. In DLB brains, mTor was more abundant in neurons displaying alpha-synuclein accumulation. These neurons also showed abnormal expression of lysosomal markers such as LC3, and ultrastructural analysis revealed the presence of abundant and abnormal autophagosomes. Similar alterations were observed in the brains of alpha-synuclein transgenic mice. Intra-cerebral infusion of rapamycin, an inhibitor of mTor, or injection of a lentiviral vector expressing Atg7 resulted in reduced accumulation of alpha-synuclein in transgenic mice and amelioration of associated neurodegenerative alterations. Conclusions/significance This study supports the notion that defects in the autophagy pathway and more specifically in mTor and Atg7 are associated with neurodegeneration in DLB cases and alpha-synuclein transgenic models and supports the possibility that modulators of the autophagy pathway might have potential therapeutic effects.
Key findings
- Recent evidence suggests that impairment of lysosomal pathways (i.e. autophagy) involved in alpha-synuclein clearance might play an important role.
- Methodology/principal findings By immunoblot analysis, compared to controls and AD, in DLB cases levels of mTor were elevated and Atg7 were reduced.
- Levels of other components of the autophagy pathway such as Atg5, Atg10, Atg12 and Beclin-1 were not different in DLB compared to controls.
- These neurons also showed abnormal expression of lysosomal markers such as LC3, and ultrastructural analysis revealed the presence of abundant and abnormal autophagosomes.
- Conclusions/significance This study supports the notion that defects in the autophagy pathway and more specifically in mTor and Atg7 are associated with neurodegeneration in DLB cases and alpha-synuclein transgenic models and supports the possibility that modulators of the autophagy pathway might have potential therapeutic effects.
Why it matters
In brains from people with dementia with Lewy bodies, levels of mTor were elevated and Atg7 reduced compared with controls and Alzheimer's disease, and similar changes appeared in alpha-synuclein transgenic mice, where rapamycin or an Atg7 vector reduced alpha-synuclein accumulation. This is tissue and animal work on autophagy, not a treatment tested in patients.
Study details
- Evidence strengthLow
How this study scored 16/100
Retracted — do not rely on it. It scored 32 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (PloS one) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 0 / 10 | Retracted — do not rely on it. PubMed indexes it as a Retracted Publication. |
| How recent | 1 / 5 | 2010 — 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 | 6 / 7 | Cited 368 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.4 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 4 / 6 | Cited 16.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 37 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Eliezer Masliah: h-index 195 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20174468) |
| Free to read | 2 / 2 | Free to read |
| Total | 32 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Crews, L., Spencer, B., Desplats, P., Patrick, C., Paulino, A., Rockenstein, E., et al. (2010). Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy. PloS one. https://doi.org/10.1371/journal.pone.0009313
Vancouver
Crews L, Spencer B, Desplats P, Patrick C, Paulino A, Rockenstein E, et al. Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy. PloS one. 2010. doi:10.1371/journal.pone.0009313. PMID: 20174468.
BibTeX
@article{crews2010-20174468,
author = {Crews, L. and Spencer, B. and Desplats, P. and Patrick, C. and Paulino, A. and Rockenstein, E. and Hansen, L. and Adame, A. and others},
title = {{Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy}},
journal = {PloS one},
year = {2010},
doi = {10.1371/journal.pone.0009313},
pmid = {20174468},
url = {https://doi.org/10.1371/journal.pone.0009313}
}
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