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Upon identification of several isoforms of amyloid precursor protein ( APP ) mRNA with a deletion followed by an insertion that accounted for epigenetic control of genomic rearrangements of APP gene in fibroblasts of patients with LNS, Nguyen proposed a role of epistasis between mutated HPRT1 and APP genes affecting the regulation of alternative APP pre-mRNA splicing as a possible pathophysiological mechanism of the severe neurobehavioral phenotype of LNS ( Cerebral Creatine Deficiency Syndromes Creatine serves as a donor of high-energy phosphates for the synthesis of hydrolyzed adenosine triphosphate

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C.HotchkissM.FerrellJ.JayaramanS.MillsL.ModicW.et al (2009)

Additionally, it downregulated the expression of ionized calcium-binding adapter molecule 1 (Iba-1), inhibited spinal cord ferroptosis and inflammatory responses, and improved gait abnormalities and limb weakness in EAE mice