Ask about this productRelated genes to: TIA1 antibody
- Gene:
- TIA1 NIH gene
- Name:
- TIA1 cytotoxic granule associated RNA binding protein
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 2p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1995-11-01
- Date modifiied:
- 2016-10-05
Related products to: TIA1 antibody
Related articles to: TIA1 antibody
- Chronic pain is a widespread and debilitating condition, presenting significant clinical, socio-economic, and public health challenges. Microglia, the resident immune cells of the central nervous system, are implicated in the regulation of chronic pain, but the precise mechanisms, particularly brain region-specific contributions, remain poorly understood. In this study, we used a mouse model of complete Freund's adjuvant (CFA)-induced inflammatory pain to explore the role of T-cell intracellular antigen 1 (TIA1), an RNA-binding protein, in microglia. We found that conditional knockout of Tia1 in microglia (Tia1-CKO mice) resulted in a significant reduction in pain sensitivity. Notably, the lateral septum (LS) emerged as a key brain region, where microglial activation was most significantly elevated in response to CFA-induced inflammation. Mechanistically, we discovered that TIA1 binds to and suppresses the translation of IκBα mRNA, triggering NF-κB signaling that contributes to neuroinflammation and neuronal hyperexcitability in the LS. In Tia1-CKO mice, chronic pain was alleviated, accompanied by restored IκBα expression and reduced NF-κB activation in the LS. In contrast, forced degradation of IκBα in the LS of these pain-resistant mice reinstated NF-κB activity and reversed the analgesic effects. These findings uncover a previously unknown post-transcriptional mechanism in microglia, where TIA1 links RNA-binding protein activity to NF-κB-driven neuroinflammation. Our results underscore the lateral septum as a critical region in chronic pain persistence and highlight TIA1 as a promising therapeutic target for intervention. - Source: PubMed
Publication date: 2026/04/22
Liu FuruiXue XiuminLi HongyanHe ZiwanWang RuiyiGuo YueWang Yongjie - Alzheimer's disease (AD) is characterized by proteostasis collapse driven by amyloid-β (Aβ) plaques and tau tangles. Dysregulation of stress granule (SG) dynamics and aberrant histone deacetylase 6 (HDAC6) activity are emerging as pivotal pathogenic mechanisms promoting neurodegeneration. Here, we identify that Cucurbitacin B (CB), a natural triterpenoid, acts as a potent SG inducer that confers broad-spectrum neuroprotection. Mechanistically, we demonstrate a novel "recruit-and-sequester" model: CB promotes the assembly of HDAC6-recuited SGs, thereby physically sequestering HDAC6 and functionally inhibiting its deacetylase activity. In Caenorhabditis elegans (C. elegans) and mammalian cell models, CB treatment significantly alleviated Aβ oligomer-induced cytotoxicity and tau hyperphosphorylation. Notably, the neuroprotective efficacy of CB was abolished by the genetic knockdown of core SG components (gtbp-1/G3BP1, tiar-1/TIA1) or hda-6/HDAC6, confirming that its therapeutic action relies on the integrity of the HDAC6-SG. Our findings highlight the potential of modulating SG dynamics to spatially regulate HDAC6, offering a novel therapeutic strategy for AD. - Source: PubMed
Publication date: 2026/04/21
Tu XiaohuiFang MinglvYan YingxuanLiu YingYu JingChen LiangZhang LuHuang ChengFan Shengjie - Recent studies indicate that levels of Advanced Oxidation Protein Products (AOPPs) in the synovial fluid of osteoarthritis (OA) patients positively correlate with disease severity. AOPPs are not only biomarkers of oxidative damage but also effector molecules that drive disease progression. Although stress granules (SGs) play a central role in cellular stress response, their function in AOPPs-mediated OA progression remains unclear. This study is the first to reveal the signaling pathway through which AOPPs exacerbate OA by disrupting SGs assembly. We found that AOPPs disrupt intracellular calcium homeostasis, induce endoplasmic reticulum stress (ERS), and subsequently activate the PERK-ATF4-CHOP signaling axis. This activation upregulates the key regulator GADD34. Increased GADD34 leads to abnormal dephosphorylation of eIF2α, which hinders the nucleocytoplasmic transport of the core SGs protein TIA-1 and ultimately disrupts SGs assembly. Further experiments demonstrated that the GADD34-specific inhibitor Sephin1 effectively restores eIF2α phosphorylation and rebuilds SGs formation, significantly alleviating OA progression. Moreover, we innovatively developed a hyaluronic acid microneedles transdermal delivery system loaded with Sephin1. In vivo studies confirmed that its efficacy is comparable to intra-articular injection, while offering the advantages of being minimally invasive and safe. This research not only elucidates a novel mechanism of the AOPPs-ERS-SGs axis in OA pathogenesis but also provides a new therapeutic target and delivery strategy for OA treatment. - Source: PubMed
Publication date: 2026/04/18
Jiang WeihaoWang QiZhang XvQi BeijieLiang YonghuiLi DeijianYi Chengqing - - Source: PubMed
Publication date: 2026/04/17
Niss FridaPiñero-Paez LauraZaidi WajihaHallberg EinarStröm Anna-Lena - Opioid and methamphetamine use disorders (OUD and MUD) are characterized by enduring neural adaptations within brain reward circuitry, yet the cell-type-specific post-transcriptional mechanisms underlying these changes remain poorly understood. While microglia are essential for maintaining central nervous system homeostasis and modulating neuroinflammatory responses to drugs of abuse, their alternative splicing (AS) programs have not been defined in the context of addiction. This study characterized the microglial AS landscape in the mouse dorsal striatum during morphine and methamphetamine intravenous self-administration (IVSA), as well as following a 21-day period of abstinence. Analysis of RNA-sequencing data using rMATS and DEXSeq revealed that both drugs significantly dysregulate core splicing machinery, with skipped exons (SE) emerging as the most prevalent splicing event. Notably, morphine exposure induced a robust persistent splicing signature, comprising 736 exonic regions in 221 genes that remained altered through abstinence, whereas methamphetamine-induced changes were primarily reversible. Functional annotation predicted that approximately 27.5% of these events induce frameshifts, potentially impacting critical microglial pathways such as autophagy (), chromatin remodeling (), and RNA processing (). These findings identify previously unrecognized post-transcriptional neuroimmune mechanisms and suggest that persistent splicing dysregulation in microglia may contribute to the long-term pathophysiology of OUD. - Source: PubMed
Publication date: 2026/04/05
Margetts Alexander VBystrom Lauren LVilca Samara JTuesta Luis M