التفاصيل البيبلوغرافية
| العنوان: |
Annexin A11 mutations are associated with nuclear envelope dysfunction in vivo and in human tissues. |
| المؤلفون: |
Marchica, Valentina, Biasetti, Luca, Barnard, Jodi, Li, Shujing, Nikolaou, Nikolas, Frosch, Matthew P, Lucente, Diane E, Eldaief, Mark, King, Andrew, Fanto, Manolis, Troakes, Claire, Houart, Corinne, Smith, Bradley N |
| المصدر: |
Brain: A Journal of Neurology; Jan2025, Vol. 148 Issue 1, p276-290, 15p |
| مصطلحات موضوعية: |
AMYOTROPHIC lateral sclerosis, NUCLEAR membranes, ANNEXINS, ABNORMALITIES in animals, FRONTOTEMPORAL dementia |
| مستخلص: |
Annexin A11 mutations are a rare cause of amyotrophic lateral sclerosis (ALS), wherein replicated protein variants P36R, G38R, D40G and D40Y are located in a small helix within the long, disordered N-terminus. To elucidate disease mechanisms, we characterized the phenotypes induced by a genetic loss-of-function and by misexpression of G38R and D40G in vivo. Loss of Annexin A11 results in a low-penetrant behavioural phenotype and aberrant axonal morphology in zebrafish homozygous knockout larvae, which is rescued by human wild-type Annexin A11. Both Annexin A11 knockout/down and ALS variants trigger nuclear dysfunction characterized by Lamin B2 mislocalization. The Lamin B2 signature also presented in anterior horn, spinal cord neurons from post-mortem ALS ± frontotemporal dementia patient tissue possessing G38R and D40G protein variants. These findings suggest mutant Annexin A11 acts as a dominant negative, revealing a potential early nucleopathy highlighting nuclear envelope abnormalities preceding behavioural abnormality in animal models. [ABSTRACT FROM AUTHOR] |
|
Copyright of Brain: A Journal of Neurology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |