ATP13A2
- Known as:
- ATP13A2
- Catalog number:
- 002273A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ATP13A2
Related genes to: ATP13A2
- Gene:
- ATP13A2 NIH gene
- Name:
- ATPase cation transporting 13A2
- Previous symbol:
- PARK9
- Synonyms:
- HSA9947, CLN12
- Chromosome:
- 1p36.13
- Locus Type:
- gene with protein product
- Date approved:
- 2005-01-12
- Date modifiied:
- 2019-04-23
Related products to: ATP13A2
Related articles to: ATP13A2
- Polyamines (PAs), principally putrescine (Put), spermidine (Spd), and spermine (Spm), are ubiquitous aliphatic polycations that regulate nucleic-acid interactions, ion-channel activity, autophagy, redox balance, proteostasis, and immune signaling. Growing genetic, multi-omics, and experimental evidence indicates that disruption of PA biosynthesis, catabolism, acetylation, and transport contributes to neurological disease. In Alzheimer's disease (AD), altered PA flux intersects with Tau and amyloid-β (Aβ) pathology, methylation imbalance, oxidative stress, and impaired autophagic clearance. In Parkinson's disease (PD), PA transport and interconversion are linked to lysosomal dysfunction, mitochondrial stress, and α-synuclein toxicity; ATP13A2-associated Kufor-Rakeb syndrome further illustrates the neurological consequences of defective lysosomal PA transport. PA dysregulation is also implicated in amyotrophic lateral sclerosis (ALS), diabetic retinopathy, Snyder-Robinson syndrome, epilepsy, Bachmann-Bupp syndrome, and cerebral ischemia. This review integrates disease-specific evidence with four interconnected mechanisms-autophagy, oxidative stress, proteostasis, and neuroinflammation-and discusses therapeutic approaches including direct Spd administration, modulation of PA-metabolic enzymes and transporters, and combination strategies. Because PAs can exert both protective and toxic effects depending on concentration, cellular compartment, and disease context, translation will require CNS-relevant biomarkers, dose and route optimization, and explicit consideration of blood-brain barrier constraints. - Source: PubMed
Publication date: 2026/09/22
Li KehuaSi QiongyaZhang ChunxiangZhang ChaojieWang MengyaoLiu JingnanZhao JianhuaXing HongxiaLiu Junli - ATP13A2 is a lysosomal P5B-type ATPase whose loss-of-function mutations are associated with a spectrum of neurodegenerative disorders, including early-onset Parkinson's disease, Kufor-Rakeb syndrome, neuronal ceroid lipofuscinosis, hereditary spastic paraplegia, and amyotrophic lateral sclerosis. Although ATP13A2 is known to contribute to lysosomal homeostasis and, thereby, to neuronal degeneration, emerging evidence suggests that it may also influence exosome biology. However, the mechanisms by which endogenous ATP13A2 regulates exosome biogenesis and the relevance of this process to neuronal vulnerability remain unclear. In the present study, using multiple ATP13A2-deficient human cell models, we demonstrated that ATP13A2 deficiency impairs intraluminal vesicle (ILV) biogenesis and reduces exosome secretion across diverse cellular contexts. Loss of ATP13A2 did not markedly affect endocytosis, early endosome abundance, or multivesicular body formation, but it consistently reduced ILV density within multivesicular bodies. Mechanistically, ATP13A2 deficiency promoted lysosome-associated accumulation of the E3 ubiquitin ligase ITCH, which enhanced ubiquitin-proteasome-dependent degradation of ALG-2-interacting protein X (ALIX), a critical adaptor of the endosomal sorting complex required for transport machinery that mediates ILV membrane remodeling. Restoration of ALIX expression or reduction of Itchy E3 ubiquitin-protein ligase (ITCH) activity rescued the ILV biogenesis defects in ATP13A2-deficient neuronal cells. Furthermore, dysregulation of the ATP13A2-ITCH-ALIX pathway increased neuronal susceptibility to mitochondrial stress, whereas restoration of ALIX or reduction of ITCH activity markedly improved neuronal survival. Together, these results identify an ATP13A2-ITCH-ALIX signaling axis linking lysosomal dysfunction to impaired ILV biogenesis and exosome regulation. Our study suggests that defective ILV biogenesis contributes to neuronal vulnerability and that modulation of the ATP13A2-ITCH-ALIX pathway may represent a therapeutic strategy for ATP13A2-associated neurodegeneration. - Source: PubMed
Publication date: 2026/09/19
Luo LinChen WenLuo ShishiMa SuzhenLiu KaiyueGong QianHuang BirongChen ZhimingHe YaohuiWang Danling - Familial Parkinson's disease (PD) and vascular parkinsonism (VP) present overlapping features and may co-exist. To investigate whether PD and VP may share a potential pathogenic link and to what extent white matter hyperintensities may influence PD phenotype, we used the modified Scheltens scale and presented a descriptive and exploratory analysis of the classic neuroradiological features of cerebral small vessel disease (cSVD) in the axial T2-FLAIR MRI sequences in a cohort of 104 familial PD and PD prodromal patients and 48 age-matched controls from the PPMI publicly available database. We next performed whole exome sequencing to examine the protein coding variability in the main PD-causing and risk genes (VPS35, DJ1, PINK1, ATP13A2, PRKN, SNCA, LRRK2, GBA, MAPT, LAMP3, STK39) in a cohort of 96 patients with familial cSVD and 243 elderly healthy individuals (HEX database). In this cohort, patients with familial and prodromal PD present a moderate burden of superficial frontal white matter hyperintensities (p-value = 3.46e-06, Bonferroni-corrected), linked to a mild reduction of motor and cognitive function and an increased LRRK2 p.G2019S and p.R1441C variant penetrance, and bilateral basal ganglia periventricular enlarged spaces (p-value = 2.64e-03, Bonferroni-corrected). Moreover, one-third of familial PD patients displayed a burden of lacunar thalamic strokes (p-value = 0.058), associated with a moderate hypokinetic-rigid syndrome. Finally, we report no known pathogenic coding variant in the main PD causative genes and risk factors in a cohort of 96 early-onset cSVD Caucasian patients. Our study adds to the understanding of potential cSVD hallmarks within this familial LRRK2, GBA and SNCA PD-PD prodromal cohort. - Source: PubMed
Publication date: 2026/09/08
Mahat BigyanMalla BimalaFoddis MarcoBeule DieterBras JoseGuerreiro RitaKola VasilisSchmitt Hans-MichaelEndres MatthiasSassi Celeste - Polyamines, primarily spermidine and spermine, are small polycationic molecules essential for cell growth, signaling, and survival. Through electrostatic interactions with nucleic acids, lipids, and proteins, they regulate gene expression, organelle function, and adaptive responses to environmental cues. Polyamine metabolism also intersects with a myriad of other cellular pathways, including methionine, acetyl-CoA, and oxidative stress pathways, and is therefore involved in epigenetic control, cellular metabolism, and stress-response regulation. In the brain, beyond these general cellular functions, polyamines act as dynamic modulators of neurodevelopment, neural maintenance, and synaptic plasticity by influencing local proteostasis, transmitter release, and ion channel activity in both neurons and glia. Emerging evidence indicates that disruption of polyamine homeostasis contributes to neurological disorders as diverse as rare inborn errors of metabolism and common neurodegenerative diseases. Mutations in polyamine metabolic or transport genes lead to syndromes characterized by intellectual disability, hypotonia, movement disorders, and neurodegeneration; therefore, polyamine balance is critical for brain development and maintenance. In conditions such as Alzheimer's and Parkinson's diseases, dysregulated polyamine synthesis, catabolism, or lysosomal transport perturbs autophagic flux and proteostasis, thereby promoting Tau and α-synuclein aggregation, oxidative stress, and neuronal loss. Multi-omics analyses have further revealed that polyamine metabolism shapes glial inflammatory responses. Therapeutically, modulation of polyamine metabolism offers multiple intervention points. Spermidine supplementation or administration of polyamine analogues has been found to enhance autophagy and improve cognitive performance in models of aging and Alzheimer's disease. Additional strategies to reestablish metabolic equilibrium and support neuronal resilience include targeted manipulation of key enzymes, such as ornithine decarboxylase 1 (ODC1), spermidine/spermine acetyltransferase 1 (SAT1), spermine oxidase (SMOX), and spermine synthase (SMS), or restoration of lysosomal polyamine export via ATP13A2. This review synthesizes current understanding of polyamine metabolism in brain health and disease, by integrating molecular, cellular, and systems-level perspectives, and further highlights emerging therapeutic directions aimed at harnessing this pathway to mitigate neurological pathology. - Source: PubMed
Publication date: 2026/02/27
Tao XianzunNassuna TraceyZhai R Grace - Liver hepatocellular carcinoma (LIHC) is a molecularly heterogeneous malignancy for which additional genetically supported biomarkers and functional regulators remain to be identified. We aimed to identify candidate genes through integrative genetic and transcriptomic screening, then determine the cellular context and functional relevance of the leading candidate. We applied Summary-data-based Mendelian Randomization to FinnGen LIHC genome-wide association summary statistics and GTEx v8 liver cis-eQTL summary data. A 1000 Genomes European-ancestry panel provided the linkage disequilibrium reference. Candidate genes were cross-referenced with Gene Expression Omnibus differentially expressed genes and TCGA-LIHC prognostic genes. After ATP13A2 emerged from this screen, we used bulk, single-cell, and spatial transcriptomic analyses to characterize its expression and cellular context. HUVEC knockdown, migration, tube formation, qRT-PCR, and Western blotting were then used for functional assessment. ATP13A2 was the only gene shared by the SMR-prioritized, GEO differential-expression, and TCGA-LIHC prognostic sets. ATP13A2 expression was higher in LIHC tissues and independently associated with worse survival in the TCGA-LIHC cohort. Single-cell analysis subsequently localized ATP13A2 predominantly to tumor endothelial cells, and spatial and pathway analyses associated ATP13A2-positive endothelial cells with angiogenic programs and inferred PTN-NCL signaling. In HUVECs, ATP13A2 knockdown reduced migration and tube formation and was accompanied by reduced ERK1/2 and p38 MAPK phosphorylation. An unbiased integrative screen prioritized ATP13A2 as a genetically supported LIHC candidate, after which single-cell analysis identified its tumor-endothelial context. Functional knockdown data support an association with endothelial angiogenic phenotypes. Rescue, in vivo, and independent clinical validation remain required. - Source: PubMed
Publication date: 2026/08/10
Liu QiLiu YuyangChen JunyiWan TaoLi ChaoYang ZhanyuZhang Ning