Molecular and clinical characteristics of ATP1A3-related diseases

Abstract

ObjectiveWith detailed studies of ATP1A3-related diseases, the phenotypic spectrum of ATP1A3 has greatly expanded. This study aimed to potentially identify the mechanisms by which ATP1A3 caused neurological dysfunction by analyzing the clinical features and phenotypes of ATP1A3-related diseases, and exploring the distribution patterns of mutations in the subregions of the ATP1A3 protein, thus providing new and effective therapeutic approaches.MethodsDatabases of PubMed, Online Mendelian Inheritance in Man, and Human Gene Mutation Database, Wanfang Data, and Embase were searched for case reports of ATP1A3-related diseases. Following case screening, we collected clinical information and genetic testing results of patients, and analyzed the disease characteristics on the clinical phenotype spectrum associated with mutations, genetic characteristics of mutations, and effects of drug therapy.ResultsWe collected 902 clinical cases related to ATP1A3 gene. From the results of previous studies, we further clarified the clinical characteristics of ATP1A3-related diseases, such as alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism; cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome, and relapsing encephalopathy with cerebellar ataxia, frequency of mutations in different phenotypes and their distribution in gene and protein structures, and differences in mutations in different clinical phenotypes. Regarding the efficacy of drug treatment, 80 of the 124 patients with AHC were treated with flunarizine, with an effectiveness rate of ~64.5%.ConclusionsNervous system dysfunction due to mutations of ATP1A3 gene was characterized by a group of genotypic–phenotypic interrelated disease pedigrees with multiple clinical manifestations. The presented results might help guide the diagnosis and treatment of ATP1A3-related diseases and provided new ideas for further exploring the mechanisms of nervous system diseases due to ATP1A3 mutations.

ATP1A3 regulates protein synthesis for mitochondrial stability under heat stress

“…These data never exclude the established concept that Na + /K + -ATPase activities of Atp1a3 play indispensable roles in the maintenance of cell viability, resting and action potential formation in neurons, and their mitochondrial energy production in vivo ( Arystarkhova et al, 2019 ; de Lores Arnaiz and Ordieres, 2014 ; Heinzen et al, 2014 ; Li et al, 2022 ). However, the results support an alternative hypothesis that Atp1a3 maintains the mitochondrial membrane potential through Na + /K + -ATPase-independent mechanisms.…”

CAPOS Syndrome with Fluctuating Symptoms

“…Retrospective analysis has found that the use of steroids, amantadine, or acetazolamide can lead to symptomatic improvement in some CAPOS patients. 20 Since oral ATP, aripiprazole, and topiramate can be beneficial in AHC, and trihexyphenidyl and amantadine have been used in some patients with RDP, these may be considered in CAPOS as well. 20 Unfortunately, several medication trials were either not tolerated or were ineffective in our patient.…”

“…20 Since oral ATP, aripiprazole, and topiramate can be beneficial in AHC, and trihexyphenidyl and amantadine have been used in some patients with RDP, these may be considered in CAPOS as well. 20 Unfortunately, several medication trials were either not tolerated or were ineffective in our patient. Thus, spells were controlled mainly with activity modulation.…”

Widespread Involvement of Acetylation in the Retinal Metabolism of Form-Deprivation Myopia in Guinea Pigs

“…In particular, proteins with significantly downregulated levels of Kac included the ATPase Na + /K + transport subunits α1/α3/β1 (ATP1A1/ATP1A3/ATP1B1). All three proteins above belong to the Na + /K + -ATPase subfamily, and Na + /K + -ATPase was a complete membrane protein which established and maintained the electrochemical gradient of Na + and K + crossing the plasma membrane . Liang et al and Crewther et al also used scanning electron microscopy and elemental microanalysis to prove that Na + and K + concentrations in the ocular posterior pole increased after form deprivation.…”

“…All three proteins above belong to the Na + /K + -ATPase subfamily, and Na + /K + -ATPase was a complete membrane protein which established and maintained the electrochemical gradient of Na + and K + crossing the plasma membrane. 56 Liang et al 57 and Crewther et al 58 also used scanning electron microscopy and elemental microanalysis to prove that Na + and K + concentrations in the ocular posterior pole increased after form deprivation. In brief, our results suggested that Kac may play a role in the regulation of water and ion homeostasis, thereby affecting FDM formation.…”