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Enhanced ATPase activities as a primary defect of mutant valosin-containing proteins that cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
Manno A, Noguchi M, Fukushi J, Motohashi Y, Kakizuka A.. Genes to cells : devoted to molecular & cellular mechanisms, 2010-07-05
Topic: Brain proteins, microglia and lab models
Valosin-containing protein (VCP) has been shown to colocalize with abnormal protein aggregates, such as nuclear inclusions of Huntington disease and Machado-Joseph disease, Lewy bodies in Parkinson disease. Several mis-sense mutations in the human VCP gene have been identified in patients suffering inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD). Recently, we have shown that VCP possesses both aggregate-forming and aggregate-clearing activities. Here, we showed that in cells treated with proteasome inhibitors VCP first appeared as several small aggregates throughout the cells; and then, these small aggregates gathered together into a single big aggregate. Subcellular localization and ATPase activity of VCP clearly influenced the localization of the aggregates. Furthermore, all tested IBMPFD-causing mutant VCPs, possessed elevated ATPase activities and enhanced aggregate-forming activities in cultured cells. In Drosophila, these mutants and VCP(T761E), a super active VCP, did not appear to spontaneously induce eye degeneration, but worsened the phenotype when co-expressed with polyglutamines. Unexpectedly, these VCPs did not apparently change sizes and the amounts of polyglutamine aggregates in Drosophila eyes. Elevated ATPase activities, thus, may be a hidden primary defect causing IBMPFD pathological phenotypes, which would be revealed when abnormal proteins are accumulated, as typically observed in aging.
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APA 7th
Manno, A., Noguchi, M., Fukushi, J., Motohashi, Y., & Kakizuka, A. (2010). Enhanced ATPase activities as a primary defect of mutant valosin-containing proteins that cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Genes to cells : devoted to molecular & cellular mechanisms. https://doi.org/10.1111/j.1365-2443.2010.01428.x
Vancouver
Manno A, Noguchi M, Fukushi J, Motohashi Y, Kakizuka A. Enhanced ATPase activities as a primary defect of mutant valosin-containing proteins that cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Genes to cells : devoted to molecular & cellular mechanisms. 2010. doi:10.1111/j.1365-2443.2010.01428.x. PMID: 20604808.
BibTeX
@article{manno2010-20604808,
author = {Manno, A. and Noguchi, M. and Fukushi, J. and Motohashi, Y. and Kakizuka, A.},
title = {{Enhanced ATPase activities as a primary defect of mutant valosin-containing proteins that cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia}},
journal = {Genes to cells : devoted to molecular \& cellular mechanisms},
year = {2010},
doi = {10.1111/j.1365-2443.2010.01428.x},
pmid = {20604808},
url = {https://doi.org/10.1111/j.1365-2443.2010.01428.x}
}
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Key findings
- Several mis-sense mutations in the human VCP gene have been identified in patients suffering inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD).
- Recently, we have shown that VCP possesses both aggregate-forming and aggregate-clearing activities.
- Here, we showed that in cells treated with proteasome inhibitors VCP first appeared as several small aggregates throughout the cells; and then, these small aggregates gathered together into a single big aggregate.
- Elevated ATPase activities, thus, may be a hidden primary defect causing IBMPFD pathological phenotypes, which would be revealed when abnormal proteins are accumulated, as typically observed in aging.
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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 (Genes to cells : devoted to molecular & cellular mechanisms) |
| 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 | 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 | — / 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 20604808) |
| 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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