Ask about this productRelated genes to: RPH3A antibody
- Gene:
- RPH3A NIH gene
- Name:
- rabphilin 3A
- Previous symbol:
- -
- Synonyms:
- KIAA0985, rabphilin, exophilin-1
- Chromosome:
- 12q24.13
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-10
- Date modifiied:
- 2015-09-07
Related products to: RPH3A antibody
Related articles to: RPH3A antibody
- Spinocerebellar Ataxia type 2 (SCA2) and Amyotrophic Lateral Sclerosis type 13 (ALS13) are triggered by polyglutamine expansion in Ataxin-2 (ATXN2). To understand these neurodegenerative disorders at the molecular level, the brains of 10-month-old -CAG100-knockin mice were analyzed as microglial, astroglial and neuronal fractions via global RNA sequencing. Data were validated by comparison with the spinal cord oligonucleotide microarray profile or filtered by RNA-seq consistency. Here, we show that the mutation causes a massive inflammatory response in microglia and a reciprocal loss of neuronal transcripts in glial fractions, suggesting severe synapse loss. Beyond these general neurodegenerative signs, we identify pathognomonic changes in the machinery for protein translation and RNA splicing. Glial fractions showed upregulation of (to 2082%), , , , , , , , and as an unspecific neuroinflammatory signature, versus downregulation of axonal (to <19%), and synaptic , , , and mRNAs correlating with circuit disconnection. In all fractions, reductions in , , and were noted versus disease-specific inductions of ribosomal subunits, presumably mirroring the partial loss-of-function of ATXN2 as RNA translation modulator. Selective accumulations of embryonic factors and versus downregulation of adult specify the mutation impact on splicing and translation elongation. As a potential underpinning of toxic gain-of-function, the proteostasis transcript appeared increased in astroglial and microglial fractions. These transcriptome data suggest altered ribosomal and spliceosome machinery, with massive microgliosis versus mild astrogliosis, at the core of SCA2 and ALS13. - Source: PubMed
Publication date: 2026/04/15
Auburger GeorgKandi Arvind ReddyVutukuri RajkumarAlmaguer-Mederos Luis-EnriqueGispert SuzanaSen Nesli-EceKey Jana - Inhibition of voltage-gated potassium channel Kv1.3 is a therapeutic strategy to curb microglia-mediated neuroinflammation in neurodegeneration, although the cellular and signaling mechanisms of disease-modification by Kv1.3 blockers are unclear. In this study, we delineate protective mechanisms of Kv1.3 blockade in a mouse model of Alzheimer's disease (AD) pathology using comprehensive transcriptomics and proteomics profiling of brain, corresponding with neuropathological effects of two translationally relevant Kv1.3 blockers, namely small molecule PAP-1 and peptide ShK-223. Following 3 months of treatment, both molecules reduced Ab plaque burden. Single nuclear RNA seq (snRNA seq) of brain nuclei showed that PAP-1 disproportionately impacted oligodendrocytes and microglia and increased crosstalk between neurons and astrocytes with endothelial cells. In contrast, ShK-223 had pronounced effects on glutamatergic neurons and astrocytes. Both blockers increased expression of myelination genes in oligodendrocytes and synaptic genes in neurons. Neuroprotective effects of PAP-1 were further confirmed by bulk brain transcriptomics and proteomics whereby PAP-1 increased levels of synaptic, cognitive resilience and mitochondrial proteins, while decreasing glial and immune pathways including STAT1/3 phosphorylation. Using proximity labeling and co-immunoprecipitation, we found that Kv1.3 interacts with STAT1/3 in microglia. Using microglial cell lines and primary microglia, we discovered a preferential functional coupling between Kv1.3 and type 2 but not type 1 IFN signaling. Brain-level disease modification by Kv1.3 blockade was reflected in the cerebrospinal fluid (CSF) via reduced levels of neurofilament-light (NEFL) and resilience protein RPH3A, both of which are increased in human AD CSF. Together, this study demonstrates functional links between Kv1.3 channels and type 2 IFN signaling and reveals distinct cellular effects of Kv1.3 blockers in AD pathology that correspond with reduced neuropathology and neuroinflammation, augmentation of resilience and neuro-vascular pathways, along with biomarkers of therapeutic effect. - Source: PubMed
Publication date: 2025/12/25
Kumari RashmiBowen ChristineSrivastava UpasnaBrandelli Amanda DabdabKumar PrateekKour DilpreetMalepati SnehaJang Wooyoung EricBromwich MarkZeng HollisSing AnsonSloan Steven AWulff HeikeRangaraju Srikant - Lymphocytic hypophysitis (LYH) is a rare autoimmune disorder characterized by lymphocytic infiltration of the pituitary gland, leading to central diabetes insipidus (CDI) and hypopituitarism. Although distinguishing LYH from other diseases presenting with pituitary enlargement is challenging, the use of anti-rabphilin-3A antibody (RPH3A-Ab) in the diagnosis of LYH has been recently reported. Case reports of LYH following coronavirus disease 2019 (COVID-19) infection in adult and adolescent patients have been accumulated. Here, we present the first case confirming the presence of RPH3A-Abs in pediatric CDI following COVID-19. A 4-yr-old girl developed CDI one week after COVID-19, and anterior hypopituitarism was confirmed 14 mo later. Head magnetic resonance imaging (MRI) revealed progressive pituitary stalk thickening, which subsequently improved. Although other disease-specific markers did not increase, serological testing confirmed the presence of RPH3A-Ab, supporting the clinical diagnosis of LYH. It has previously reported that RPH3A-Ab demonstrate high sensitivity and specificity in differential diagnosis of LYH, and RPH3A-Ab are also identified as positive in pediatric cases of LYH with a biopsy. Additionally, this is the first documented prepubertal case of LYH following COVID-19. Our case study indicates that LYH can occur in children after COVID-19, and RPH3A-Ab may be useful in its diagnosis. - Source: PubMed
Publication date: 2025/08/29
Fukuta TaroFukasawa TatsuyaMizutani HarukiKato ShunsukeIshikawa TakuyaFukushima MaiIwata NaokoFujisawa HarukiSuzuki AtsushiSugimura YoshihisaHamajima Takashi - Heat stress (HS) is a major environmental factor negatively impacting the reproductive performance of livestock. This study investigates the molecular mechanisms of heat stress on the hypothalamic-pituitary-ovarian (HPO) axis in Hu sheep. A heat-stressed animal model was established, and high-throughput RNA sequencing (RNA-seq) was employed to analyze gene expression in the hypothalamus, pituitary, and ovarian tissues of both control and heat-stressed groups. The results revealed significant changes in estrus behavior, hormone secretion, and reproductive health in heat-stressed sheep, with a shortened estrus duration, prolonged estrous cycles, and decreased levels of FSH, LH, E, and P4. A total of 520, 649, and 482 differentially expressed genes (DEGs) were identified in the hypothalamus, pituitary, and ovary, respectively. The DEGs were enriched in pathways related to hormone secretion, neurotransmission, cell proliferation, and immune response, with significant involvement of the p53 and cAMP signaling pathways. Tissue-specific responses to heat stress were observed, with distinct regulatory roles in each organ, including GPCR activity and cytokine signaling in the hypothalamus, calcium-regulated exocytosis in the pituitary, and cilium assembly and ATP binding in the ovary. Key genes such as , , and were identified as central to the coordinated regulation of the HPO axis. These findings provide new insights into the molecular basis of heat stress-induced impairments in reproductive function-manifested by altered estrous behavior, reduced hormone secretion (FSH, LH, E, and P4), and disrupted gene expression in the hypothalamic-pituitary-ovarian (HPO) axis-and offer potential targets for improving heat tolerance and reproductive regulation in sheep. - Source: PubMed
Publication date: 2025/07/25
Zou JianweiWei LiliLiang YishanZou JuhongCheng PengfeiMo ZhihuaSun WenyueWei YirongLu JunLi WenmanShen YulongDeng XiaoyanHuang YannaJiang Qinyang - Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by compromised neuromuscular signal transmission due to pathogenic germline variants in genes expressed at the neuromuscular junction (NMJ). A total of 40 genes have been reported in CMS (AGRN, ALG14, ALG2, CHAT, CHD8, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, COL13A1, COLQ, DES, DOK7, DPAGT1, GFPT1, GMPPB, LAMA5, LAMB2, LRP4, MACF1, MUSK, MYO9A, PLEC, PREPL, PTPN11, PURA, RAPSN, RPH3A, SCN4A, SLC18A3, SLC25A1, SLC5A7, SNAP25, SYT2, TEFM, TOR1AIP1, UNC13A, UNC50 and VAMP1). The 40 genes are putatively classified into 13 subtypes by pathomechanical, clinical, and therapeutic features. A unique feature shared by recently identified genes is that CMS is concomitantly recognized in other mostly severer diseases. For example, four recently identified genes exhibit the following phenotypes: PURA-CMS, developmental delay; TEFM-CMS, mitochondrial disease; PTPN11-CMS, Noonan syndrome/Leopard syndrome; and DES-CMS, desmin myopathy. Conversely, these diseases are not always associated with CMS, although genetic and/or environmental factors that determine the involvement of the NMJ remain to be identified. In this review, particular emphasis will be placed on five recently identified genes (MACF1, TEFM, PTPN11, DES and UNC50). - Source: PubMed
Publication date: 2025/06/18
Ohno KinjiIto MikakoOhkawara Bisei