m6A-centered Disease Response Information

General Information of the Disease (ID: M6ADIS0135)
Name
Motor neuron disease
ICD
ICD-11: 8B60
Full List of Target Gene(s) of This m6A-centered Disease Response
Histone deacetylase 4 (HDAC4)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary ALKBH5 demethylates and stabilizes Hdac4 mRNA. Histone deacetylase 4 (HDAC4) interacts with and deacetylates FoxO3, resulting in a significant increase in FoxO3 expression. These results suggest that ALKBH5 is a potential therapeutic target for neurogenic muscle atrophy.
Responsed Disease Progressive muscular atrophy [ICD-11: 8B60.3]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
In-vivo Model Mice bearing the Alkbh5-floxed allele (Alkbh5 fl/fl , Cyagen) were crossed with transgenic mice expressing Cre recombinase under the control of the Myl1 promoter (Myl1-Cre; Stock No: 024713, The Jackson Laboratory) to generate muscle-specific Alkbh5 knockout mice (Myl1-Cre;Alkbh5 fl/fl ). Littermate Alkbh5fl/fl mice were used as controls. Genotyping by tail DNA and PCR were performed at 4 weeks of age.
PncRNA-D
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary Translocated in LipoSarcoma/Fused in Sarcoma (TLS/FUS) is a nuclear RNA binding protein whose mutations cause amyotrophic lateral sclerosis. The binding specificity of TLS/FUS to short RNA fragments derived from PncRNA-D, both wild type and ALS-related TLS/FUS mutants demonstrated stronger binding to m6A-modified RNA fragments.
Responsed Disease Amyotrophic lateral sclerosis [ICD-11: 8B60.0]
In-vitro Model HAP1 Chronic myelogenous leukemia Homo sapiens CVCL_Y019
References
Ref 1 m(6) A demethylase ALKBH5 drives denervation-induced muscle atrophy by targeting HDAC4 to activate FoxO3 signalling. J Cachexia Sarcopenia Muscle. 2022 Apr;13(2):1210-1223. doi: 10.1002/jcsm.12929. Epub 2022 Feb 9.
Ref 2 m(6)A Modified Short RNA Fragments Inhibit Cytoplasmic TLS/FUS Aggregation Induced by Hyperosmotic Stress. Int J Mol Sci. 2021 Oct 12;22(20):11014. doi: 10.3390/ijms222011014.