Ask about this productRelated genes to: SHANK1 antibody
- Gene:
- SHANK1 NIH gene
- Name:
- SH3 and multiple ankyrin repeat domains 1
- Previous symbol:
- -
- Synonyms:
- SSTRIP, SPANK-1, synamon
- Chromosome:
- 19q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 2002-02-22
- Date modifiied:
- 2016-10-05
Related products to: SHANK1 antibody
Related articles to: SHANK1 antibody
- Despite the substantial variability in physical function among older adults, the molecular mechanisms remain poorly characterized, particularly within skeletal muscle. This study aimed to determine the patterns of DNA methylation in skeletal muscle associated with physical function in healthy older adults. We analyzed DNA methylation (EPIC v2 array; 875,554 CpG sites) in skeletal muscle from 92 healthy older adults (median age 74; 62% female). Associations were examined across five phenotypes: Short Physical Performance Battery (SPPB), 6-min walk test (6MWT), handgrip strength, perceived disability (PAT-D), and lifestyle health (modified Life's Essential 8). Linear regression models adjusted for age, sex, race, BMI, and muscle fiber composition. Genomic inflation corrected via the BACON method (FDR < 0.05). Gene set enrichment analysis was performed on suggestive hits (FDR < 0.1). We identified significant differentially methylated probes (DMPs) and regions (DMRs) across all phenotypes: SPPB (70 DMPs, 22 DMRs), 6MWT (16 DMPs, 566 DMRs), handgrip strength (2 DMRs), PAT-D (19 DMPs, 1 DMR), and lifestyle health (2 DMPs). DMRs largely overlapped promoters. Identified genes overlapped known musculoskeletal and neurological GWAS hits, including RUNX2 and FOXL1 (bone mineral density), IGFBP3 (muscle mass), and NEK1 and SHANK1 (neurological function). Enrichment analysis revealed that 6MWT-associated genes relate to nervous and skeletal system development, while handgrip-associated genes involve cytoskeletal dynamics and protein assembly. Epigenetic variation in aging skeletal muscle is associated with physical function. The enrichment of pathways related to nervous and musculoskeletal development suggests specific epigenetic mechanisms underlying functional decline, offering potential targets for intervention in older adults. - Source: PubMed
Publication date: 2026/08/08
Wen XiaoxiaoChen MingjingMiao GuanhongWu ChristopherPicca AnnaTamargo Javier ALou XiangyangWu KevinAnton StephenLeeuwenburgh ChristiaanZhao Jinying - Lead (Pb) is a well-established neurotoxin that impairs motor, learning, and memory functions, particularly in children and younger adults. However, its impact on older adults remains less understood. Pb toxicity involves disruption of DNA methyltransferase activity and associated epigenetic pathways, potentially altering the expression of specific genes relevant to neurological functions. As methylation patterns naturally shift during aging, Pb exposure may induce additional neurological risks in aged populations. Using a zebrafish model, we investigated the combined effects of Pb exposure and brain aging. Two-year-old male zebrafish were exposed to 1, 10, 100, 1000, 10 000 µg/l Pb or fish water control for five days. Brain tissues were collected for DNA extraction and whole-genome bisulfite sequencing to assess global and gene-specific methylation changes. Our results found that Pb exposures ≥ 100 μg/l significantly increased global methylation levels in the aged brain. Differentially methylated genes (DMGs) exhibited methylation changes within gene body regions and were mostly annotated with ion transportation and signal transduction pathways. Although only a limited number of DMGs showed corresponding changes in gene expression, several of them were associated with locomotor-related functions, including at 10 000 Pb μg/l, and , and at 100 μg/l Pb. These findings suggest that Pb exposure during aging predominantly induces gene body-localized DNA methylation changes, and the role of such epigenetic regulation in Pb-associated neurobehavioral outcomes warrants further investigation. - Source: PubMed
Publication date: 2026/06/23
Wu Chia-ChenMeyer Danielle NWinny Grace ABanerjee DayitaBaker Tracie R - Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by the simultaneous disruption of interconnected molecular pathways, yet the structural mechanisms underlying this transcriptional disintegration remain poorly characterized. To address this, we constructed condition-specific gene co-expression networks from DLPFC bulk RNA-seq data, using a mutual-information (MI) framework with infomap community partitioning. Functional enrichment of network communities via Ingenuity Pathway Analysis (IPA) identified GABAergic signaling, SNARE complex assembly, Synaptogenesis, and neurexin and neuroligin interactions as significantly overrepresented pathways. Integration of node degree with condition-specific average expression revealed coordinated topological centralization of key synaptic genes-including NRXN2, LRRTM1, DLGAP3, and SHANK1-alongside a widespread transcriptional downregulation in GABAergic and Synaptogenesis modules. A shortest-path analysis revealed a consistent expansion of intra-pathway distances across all evaluated canonical pathways in AD, a pattern statistically consistent with reduced local co-expression cohesion. These findings reframe Late-Onset Alzheimer's Disease (LOAD) as an active structural-rewiring process, in which the observed topological centralization pattern seems to be consistent with a consolidation of co-expression around synaptic components, though we cannot exclude that shifts in cellular composition contribute to this signal in bulk RNA-seq data. - Source: PubMed
Publication date: 2026/05/27
Pinta-Castro AlejandroMichel-Ureña GabrielaPérez-González Alejandra PaulinaDe Anda-Jáuregui GuillermoHernández-Lemus Enrique - The development of ligands that modulate protein-protein interactions (PPIs) remains an ongoing challenge in chemical biology and drug discovery. While several approaches have been elaborated to target α-helix-mediated PPIs, methods for β-strand-mediated PPIs are less well developed. In addition to the shallow and extended interfaces characteristic of PPIs, β-strand-mediated PPIs exhibit topographical complexity, with side chains oriented above and below the plane of the strand, alongside hydrogen-bond donor and acceptor groups oriented perpendicular to the side chains. One class of β-strand-mediated PPIs involves the structurally conserved PDZ domains, which recognize protein partners through a β-strand containing a short consensus motif; canonical PDZ binding motifs (PBMs) recognize their substrates through a C-terminal carboxylate, offering a particularly challenging motif to mimic. Peptides and peptidomimetics represent a promising template for the design of ligands that target β-strand-mediated PPIs. In this work, we replaced segments of a peptide-based template using target/structure-agnostic fragments to achieve β-strand mimicry. Using reversible hydrazone exchange reactions allowed us to identify fragments at both the C- and N-terminus of an internal PDZ recognition motif with affinity for the SHANK1-PDZ domain. When combined into ligands bearing two different fragments, negative co-operativity was observed. In addition to broadening the acylhydrazone-fragment approach to screen for PDZ-binding ligands, this workflow for successive screening and combination of fragments should have broader applicability to other targets in future. - Source: PubMed
Publication date: 2026/04/07
Li YueGimenez DianaWarriner Stuart LWilson Andrew J - Hippocalcin (HPCA), a neuron-enriched calcium-binding protein, plays a critical role in brain function, but its role in neural precursor cells remains unclear. N-methyl-D-aspartate (NMDA) receptors are calcium-permeable glutamate receptors essential for neurodevelopment and synaptic plasticity, and their function has been implicated in neurological conditions. In this study, we investigated the role of HPCA in regulating NMDA receptor expression and function in mouse hippocampal neural precursor cells (mHNPCs). HPCA knockdown significantly reduced the expression of NMDA receptor-related genes, including , , , and selectively attenuated NMDA-induced calcium signaling. Transcriptomic analysis identified ELAV-like RNA-binding protein 3 (Elavl3), a neuron-enriched factor associated with neuronal activity, as a downstream candidate affected by HPCA knockdown. Consistently, Elavl3 suppression phenocopied HPCA deficiency, resulting in impaired NMDA receptor activity and reduced neuronal differentiation. Furthermore, hippocampal HPCA knockdown in vivo led to alterations in locomotor activity, contextual memory, and affective behaviors. Taken together, these findings demonstrate that HPCA supports NMDA receptor function and neuronal development, in part through Elavl3-associated pathways, and highlight HPCA as an important regulator of hippocampal function. - Source: PubMed
Publication date: 2026/03/06
Kang Min-JeongJung Sung JunSon HyeonHan Joong-SooPark Shin-Young