No disease-modifying treatment exists for the fatal neurodegenerative polyglutamine disease known both as Machado-Joseph disease and spinocerebellar ataxia type 3. As a potential route to therapy, we identified small molecules that reduce levels of the mutant disease protein, ATXN3. Screens of a small molecule collection, including 1250 Food and Drug Administration-approved drugs, in a novel cell-based assay, followed by secondary screens in brain slice cultures from transgenic mice expressing the human disease gene, identified the atypical antipsychotic aripiprazole as one of the hits. Aripiprazole increased longevity in a Drosophila model of Machado-Joseph disease and effectively reduced aggregated ATXN3 species in flies and in brains of transgenic mice treated for 10 days. The aripiprazole-mediated decrease in ATXN3 abundance may reflect a complex response culminating in the modulation of specific components of cellular protein homeostasis. Aripiprazole represents a potentially promising therapeutic drug for Machado-Joseph disease and possibly other neurological proteinopathies.
Pharmacology, Toxicology and Pharmaceutical Science
3
6%
Other
6
12%
Unknown
14
29%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 14. 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 2023.
All research outputs
#3,451,845
of 34,200,840 outputs
Outputs from Brain
#3,279
of 9,091 outputs
Outputs of similar age
#42,365
of 333,833 outputs
Outputs of similar age from Brain
#38
of 68 outputs
Altmetric has tracked 34,200,840 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,091 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.7. This one has gotten more attention than average, scoring higher than 63% of its peers.
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 333,833 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 68 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
