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 Alkbh5^fl/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				[3]
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

Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Disease

In total 1 item(s) under this disease
Crosstalk ID: M6ACROT03189		Crosstalk Info
m6A Regulator	RNA demethylase ALKBH5 (ALKBH5)	Regulator Info
m6A Target	Histone deacetylase 4 (HDAC4)	Target Gene
Epigenetic Regulator	Histone deacetylase 4 (HDAC4)
Regulated Target	Forkhead box protein O3 (FOXO3)
Crosstalk relationship	m6A → Histone modification

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	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 728).
Ref 3	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.