| Title |
Chronic Treatment with 17-DMAG Improves Balance and Coordination in A New Mouse Model of Machado-Joseph Disease
|
|---|---|
| Published in |
Neurotherapeutics, April 2014
|
| DOI | 10.1007/s13311-013-0255-9 |
| Pubmed ID | |
| Authors |
Anabela Silva-Fernandes, Sara Duarte-Silva, Andreia Neves-Carvalho, Marina Amorim, Carina Soares-Cunha, Pedro Oliveira, Kenneth Thirstrup, Andreia Teixeira-Castro, Patrícia Maciel |
| Abstract |
Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease currently with no treatment. We describe a novel mouse model of MJD which expresses mutant human ataxin-3 at near endogenous levels and manifests MJD-like motor symptoms that appear gradually and progress over time. CMVMJD135 mice show ataxin-3 intranuclear inclusions in the CNS and neurodegenerative changes in key disease regions, such as the pontine and dentate nuclei. Hsp90 inhibition has shown promising outcomes in some neurodegenerative diseases, but nothing is known about its effects in MJD. Chronic treatment of CMVMJD mice with Hsp90 inhibitor 17-DMAG resulted in a delay in the progression of their motor coordination deficits and, at 22 and 24 weeks of age, was able to rescue the uncoordination phenotype to wild-type levels; in parallel, a reduction in neuropathology was observed in treated animals. We observed limited induction of heat-shock proteins with treatment, but found evidence that 17-DMAG may be acting through autophagy, as LC3-II (both at mRNA and protein levels) and beclin-1 were induced in the brain of treated animals. This resulted in decreased levels of the mutant ataxin-3 and reduced intranuclear aggregation of this protein. Our data validate this novel mouse model as a relevant tool for the study of MJD pathogenesis and for pre-clinical studies, and show that Hsp90 inhibition is a promising therapeutic strategy for MJD. |
Mendeley readers
The data shown below were compiled from readership statistics for 102 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Israel | 1 | <1% |
| China | 1 | <1% |
| Brazil | 1 | <1% |
| Unknown | 99 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 23 | 23% |
| Student > Ph. D. Student | 19 | 19% |
| Student > Master | 15 | 15% |
| Student > Bachelor | 13 | 13% |
| Student > Doctoral Student | 7 | 7% |
| Other | 7 | 7% |
| Unknown | 18 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 23 | 23% |
| Biochemistry, Genetics and Molecular Biology | 20 | 20% |
| Agricultural and Biological Sciences | 18 | 18% |
| Medicine and Dentistry | 8 | 8% |
| Engineering | 3 | 3% |
| Other | 12 | 12% |
| Unknown | 18 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 June 2021.
All research outputs
#8,261,756
of 25,373,627 outputs
Outputs from Neurotherapeutics
#756
of 1,308 outputs
Outputs of similar age
#76,356
of 239,195 outputs
Outputs of similar age from Neurotherapeutics
#3
of 7 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one has received more attention than most of these and is in the 66th percentile.
So far Altmetric has tracked 1,308 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 239,195 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one. This one has scored higher than 4 of them.