| Title |
The neuroprotective transcription factor ATF5 is decreased and sequestered into polyglutamine inclusions in Huntington’s disease
|
|---|---|
| Published in |
Acta Neuropathologica, August 2017
|
| DOI | 10.1007/s00401-017-1770-2 |
| Pubmed ID | |
| Authors |
Ivó H. Hernández, Jesús Torres-Peraza, María Santos-Galindo, Eloísa Ramos-Morón, M. Rosario Fernández-Fernández, María J. Pérez-Álvarez, Antonio Miranda-Vizuete, José J. Lucas |
| Abstract |
Activating transcription factor-5 (ATF5) is a stress-response transcription factor induced upon different cell stressors like fasting, amino-acid limitation, cadmium or arsenite. ATF5 is also induced, and promotes transcription of anti-apoptotic target genes like MCL1, during the unfolded protein response (UPR) triggered by endoplasmic reticulum stress. In the brain, high ATF5 levels are found in gliomas and also in neural progenitor cells, which need to decrease their ATF5 levels for differentiation into mature neurons or glia. This initially led to believe that ATF5 is not expressed in adult neurons. More recently, we reported basal neuronal ATF5 expression in adult mouse brain and its neuroprotective induction during UPR in a mouse model of status epilepticus. Here we aimed to explore whether ATF5 is also expressed by neurons in human brain both in basal conditions and in Huntington's disease (HD), where UPR has been described to be partially impaired due to defective ATF6 processing. Apart from confirming that ATF5 is present in human adult neurons, here we report accumulation of ATF5 within the characteristic polyglutamine-containing neuronal nuclear inclusions in brains of HD patients and mice. This correlates with decreased levels of soluble ATF5 and of its antiapoptotic target MCL1. We then confirmed the deleterious effect of ATF5 deficiency in a Caenorhabditis elegans model of polyglutamine-induced toxicity. Finally, ATF5 overexpression attenuated polyglutamine-induced apoptosis in a cell model of HD. These results reflect that decreased ATF5 in HD-probably secondary to sequestration into inclusions-renders neurons more vulnerable to mutant huntingtin-induced apoptosis and that ATF5-increasing interventions might have therapeutic potential for HD. |
X Demographics
The data shown below were collected from the profiles of 12 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 3 | 25% |
| United Kingdom | 2 | 17% |
| United States | 2 | 17% |
| Portugal | 1 | 8% |
| Unknown | 4 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 9 | 75% |
| Science communicators (journalists, bloggers, editors) | 2 | 17% |
| Scientists | 1 | 8% |
Mendeley readers
The data shown below were compiled from readership statistics for 71 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 71 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 15 | 21% |
| Student > Ph. D. Student | 11 | 15% |
| Student > Master | 6 | 8% |
| Student > Doctoral Student | 5 | 7% |
| Student > Postgraduate | 5 | 7% |
| Other | 11 | 15% |
| Unknown | 18 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 14 | 20% |
| Biochemistry, Genetics and Molecular Biology | 11 | 15% |
| Neuroscience | 10 | 14% |
| Agricultural and Biological Sciences | 7 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 3% |
| Other | 6 | 8% |
| Unknown | 21 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 14 June 2018.
All research outputs
#6,391,095
of 23,567,572 outputs
Outputs from Acta Neuropathologica
#1,289
of 2,406 outputs
Outputs of similar age
#99,028
of 317,315 outputs
Outputs of similar age from Acta Neuropathologica
#12
of 24 outputs
Altmetric has tracked 23,567,572 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 2,406 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 46th percentile – i.e., 46% 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 317,315 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 68% of its contemporaries.
We're also able to compare this research output to 24 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.