| Title |
Dysregulation of a novel miR-1825/TBCB/TUBA4A pathway in sporadic and familial ALS
|
|---|---|
| Published in |
Cellular and Molecular Life Sciences, July 2018
|
| DOI | 10.1007/s00018-018-2873-1 |
| Pubmed ID | |
| Authors |
Anika M. Helferich, Sarah J. Brockmann, Jörg Reinders, Dhruva Deshpande, Karlheinz Holzmann, David Brenner, Peter M. Andersen, Susanne Petri, Dietmar R. Thal, Jens Michaelis, Markus Otto, Steffen Just, Albert C. Ludolph, Karin M. Danzer, Axel Freischmidt, Jochen H. Weishaupt |
| Abstract |
Genetic and functional studies suggest diverse pathways being affected in the neurodegenerative disease amyotrophic lateral sclerosis (ALS), while knowledge about converging disease mechanisms is rare. We detected a downregulation of microRNA-1825 in CNS and extra-CNS system organs of both sporadic (sALS) and familial ALS (fALS) patients. Combined transcriptomic and proteomic analysis revealed that reduced levels of microRNA-1825 caused a translational upregulation of tubulin-folding cofactor b (TBCB). Moreover, we found that excess TBCB led to depolymerization and degradation of tubulin alpha-4A (TUBA4A), which is encoded by a known ALS gene. Importantly, the increase in TBCB and reduction of TUBA4A protein was confirmed in brain cortex tissue of fALS and sALS patients, and led to motor axon defects in an in vivo model. Our discovery of a microRNA-1825/TBCB/TUBA4A pathway reveals a putative pathogenic cascade in both fALS and sALS extending the relevance of TUBA4A to a large proportion of ALS cases. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 51 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 13 | 25% |
| Student > Master | 12 | 24% |
| Researcher | 6 | 12% |
| Student > Bachelor | 6 | 12% |
| Student > Doctoral Student | 2 | 4% |
| Other | 3 | 6% |
| Unknown | 9 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 16 | 31% |
| Neuroscience | 10 | 20% |
| Agricultural and Biological Sciences | 4 | 8% |
| Medicine and Dentistry | 3 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
| Other | 5 | 10% |
| Unknown | 11 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. 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 06 November 2018.
All research outputs
#3,297,540
of 23,794,258 outputs
Outputs from Cellular and Molecular Life Sciences
#506
of 4,151 outputs
Outputs of similar age
#65,596
of 330,096 outputs
Outputs of similar age from Cellular and Molecular Life Sciences
#8
of 49 outputs
Altmetric has tracked 23,794,258 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,151 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one has done well, scoring higher than 87% 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 330,096 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 79% of its contemporaries.
We're also able to compare this research output to 49 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 83% of its contemporaries.