Ask about this productRelated genes to: SLAIN2 Blocking Peptide
- Gene:
- SLAIN2 NIH gene
- Name:
- SLAIN motif family member 2
- Previous symbol:
- KIAA1458
- Synonyms:
- FLJ21611
- Chromosome:
- 4p11
- Locus Type:
- gene with protein product
- Date approved:
- 2006-08-08
- Date modifiied:
- 2016-10-05
Related products to: SLAIN2 Blocking Peptide
Related articles to: SLAIN2 Blocking Peptide
- Understanding the genetic foundations of dementia is critical to unraveling its complex molecular basis. Given that a clinical diagnosis of Alzheimer's disease (AD) dementia often results from interplay between multiple underlying neuropathologic co-morbidities, previous genome-wide association studies (GWAS) of clinically diagnosed AD are restricted in their ability to translate genetic associations to potential targeted therapeutics. The current study seeks to address these limitations by presenting the largest GWAS to date (n=12,509) of neuropathologic hallmarks of AD and AD related dementias (ADRDs). We further performed a candidate-variant analysis using loci previously identified in GWAS of clinically diagnosed AD dementia and Parkinson's disease (PD). Finally, we conducted heritability and genetic correlation analyses using linkage disequilibrium (LD) score regression. We found broad genome-wide significant associations with across AD and ADRDs but not cerebrovascular disease and vascular brain injury. We further identified 12 significant loci across 10 neuropathologic phenotypes, including 5 loci previously implicated in GWAS of clinical AD and ADRDs (variants on and ) and 7 novel genome-wide associations (variants on and ). Our analysis of AD and PD clinical candidate variants demonstrated several that were associated with AD neuropathologic change and Lewy body disease, as well as substantial overlap with neuropathologic lesions other than the primary neuropathologic hallmarks of these diseases. Heritability analyses demonstrated heritability that was high for amyloid plaques (78%) relative to prior clinical AD heritability analyses, intermediate for TDP-43 inclusions (41%), and low for remaining AD and ADRD pathologic features. This study underscores the importance of investigating the underlying neuropathologic hallmarks of AD and ADRDs as a step toward refining the translation of genetic associations to biomarker interpretation and development of targeted therapeutics. - Source: PubMed
Publication date: 2026/01/23
Cholerton BrennaGodrich DanaPasteris JeremyRivero JoeMartin Eden RKunkle Brian WNaj Adam CHamilton-Nelson Kara LWang HuiLee Wan-PingDumitrescu LoganHohman Timothy JMayeux RichardLarson Eric BCrane Paul KKeene C DirkLatimer Caitlin SMukherjee ShubhabrataKofler Julia KKamboh M IlyasBennett David AMolina-Porcel LauraCuccaro MichaelPericak-Vance Margaret ARundek TatjanaScott William KKukull WalterSchellenberg Gerard Beecham Gary WMontine Thomas J - Atopic dermatitis (AD) is a chronic itchy inflammatory disease of the skin. Genetic studies have identified multiple risk factors linked to the disease; however, most of the studies have been derived from European and East Asian populations. The admixed African American (AA) genome may provide an opportunity to discovery ancestry-specific loci involved in AD susceptibility. Herein, we present joint analysis of ancestry and genotype effects followed by validation using differential gene expression analysis on AD using 726 AD-affected individuals and 999 non-AD control individuals from the AA population, genotyped using Multi-Ethnic Global Array (MEGA) followed by imputation using the Consortium on Asthma among African Ancestry Populations in the Americas (CAAPA) reference panel. The joint analysis identified two novel AD-susceptibility loci, rs2195989 in gene ANGPT1 (8q23.1) and rs62538818 in the intergenic region between genes LURAP1L and MPDZ (9p23). Admixture mapping (AM) results showed potential genomic inflation, and we implemented genomic control and identified five ancestry-of-origin loci with European ancestry effects. The multi-omics functional prioritization of variants in AM signals prioritized the loci SLAIN2, RNF39, and FOXA2. Genome-wide association study (GWAS) identified variants significantly associated with AD in the AA population, including SGK1 (rs113357522, odds ratio [OR] = 2.81), EFR3A (rs16904552, OR = 1.725), and MMP14 (rs911912, OR = 1.791). GWAS variants were common in the AA but rare in the European population, which suggests an African-ancestry-specific risk of AD. Four genes (ANGPT1, LURAP1L, EFR3A, and SGK1) were further validated using qPCR from AD and healthy skin. This study highlighted the importance of genetic studies on admixed populations, as well as local ancestry and genotype-ancestry joint effects to identify risk loci for AD. - Source: PubMed
Publication date: 2024/09/07
Gautam YaduSatish LathaRamirez StephenGrashel BrittanyBiagini Jocelyn MMartin Lisa JRothenberg Marc EKhurana Hershey Gurjit KMersha Tesfaye B - Circular RNAs (circRNAs) are circularized single-stranded ribonucleic acids that interacts with DNA, RNA, and proteins to play critical roles in cell biology. CircRNAs regulate microRNA content, gene expression, and may code for specific peptides. Indeed, circRNAs are differentially expressed in neurodegenerative disorders like Parkinson's disease (PD), playing a potential role in the mechanisms of brain pathology. The RNA molecules with aberrant expression in the brain can cross the blood-brain barrier and reach the bloodstream, which enable their use as non-invasive PD disease biomarker. Promising targets with valuable discriminatory ability in combined circRNA signatures include MAPK9_circ_0001566, SLAIN1_circ_0000497, SLAIN2_circ_0126525, PSEN1_circ_0003848, circ_0004381, and circ_0017204. On the other hand, regular exercises are effective therapy for mitigating PD symptoms, promoting neuroprotective effects with epigenetic modulation. Aerobic exercises slow symptom progression in PD by improving motor control, ameliorating higher functions, and enhancing brain activity and neuropathology. These improvements are accompanied by changes circRNA expression, including hsa_circ_0001535 (circFAM13B) and hsa_circ_0000437 (circCORO1C). The sensitivity of current methods for detecting circulating circRNAs is considered a limitation. While amplification kits already exist for low-abundant microRNAs, similar kits are needed for circRNAs. Alternatively, the use of digital PCR can help overcome this constraint. The current review examines the potential use of circRNAs as non-invasive biomarkers of PD and to assess the effects of rehabilitation. Although circRNAs hold promise as targets for PD diagnosis and therapeutics, further validation is needed before their clinical implementation. - Source: PubMed
Publication date: 2024/07/29
de Abreu Flávia Maria Camposde Oliveira Deborah Almeidade Araujo Romero Ferrari Sabrina SimplícioE Silva Karla Helena Coelho VilaçaTitze-de-Almeida RicardoTitze-de-Almeida Simoneide Souza - Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease with the cessation of matrix anabolism and aggravation of inflammation, which results in severe pain and impaired joint function. However, the mechanisms are not well understood. Circular RNAs (circRNAs) are reported to have various biological functions and participate in the development, diagnosis, prognosis, and treatment of different diseases. This study aimed to investigate the roles and mechanisms of circ-slain2 in TMJOA. We first established TMJOA mouse models and found circ-slain2 was lowly expressed in the cartilage of TMJOA through sequencing data. We observed that circ-slain2 is predominantly localized in the cytoplasm and downregulated in mouse condylar chondrocytes (mCCs) treated with tumor necrosis factor α (TNFα) and interferon γ (IFNγ). Micro-computed tomography and histological examination showed that intra-articular injection of circ-slain2 overexpressing adeno-associated virus could alleviate cartilage catabolism and synovial inflammation to relieve TMJOA in vivo. In addition, elevated circ-slain2 also showed anticatabolic and anti-inflammatory effects on IFNγ- and TNFα-stimulated mouse condylar chondrocytes (mCCs). Functional enrichment analysis indicated that protein processing in endoplasmic reticulum (ER) was associated with TMJOA, and further functional experiments confirmed that circ-slain2 could suppress ER stress in OA mCCs. RNA binding protein immunoprecipitation assay revealed an overt interaction between activating transcription factor 6 (ATF6) and circ-slain2. Inhibition of the expression of both ATF6 and circ-slain2 resulted in dilation of the ER and enhanced the expression of ER stress markers, whose ER stress level was higher than inhibition of ATF6 but lower than knockdown of circ-slain2 expression. Collectively, our research demonstrated that circ-slain2 could regulate ATF6 to relieve ER stress, reducing temporomandibular joint cartilage degradation and synovial inflammation. These findings provide prospects for developing novel osteoarthritis therapies based on circ-slain2 by focusing on reducing the inflammation of synovium and the imbalance between matrix synthesis and degradation. - Source: PubMed
Publication date: 2023/10/10
Pan XZhao ZHuang XCen X - Neuronal injury is accountable for the poor outcome of SAH patients. In this study, oxyhemoglobin (oxyHb) was used to treat cultured primary neurons to simulate SAH, while the SAH model was established by vascular puncture in mice. First, proteomics analysis and western blot assays showed Slain2 as an increased factor in neurons exposed to oxyHb treatment, which has been reported to play an important role in axonal development by regulating microtubule stability. Upregulation of neuronal Slain2 was also detected in the murine SAH model compared with sham surgery. In addition, there was no sex difference in the protein level of Slain2 in either the sham-operated or SAH groups. Furthermore, Slain2 overexpression rescued SAH-induced sensorimotor impairments in mice, while Slain2 knockdown had the opposite effect. Finally, Slain2 overexpression rescued SAH-induced axonal injury both in vivo and in vitro, which was exacerbated by Slain2 knockdown. Thus, we demonstrate here that Slain2 acts as an endogenous protective factor of neuronal axonal microtubule structure, which plays a key role in the protection against SAH-induced neuronal axonal injury. Facilitated axonal microtubule structure by Slain2 overexpression may reduce SAH-induced axonal injury and neurobehavioral dysfunction. - Source: PubMed
Publication date: 2023/09/22
Liu TingLiu YuanPeng MinLiu QianqianSi Guomin