Mouse polyclonal to SPPL2a, Host Mouse
- Known as:
- Mouse pab SPPL2a, Host Mouse
- Catalog number:
- YF-PA26751
- Product Quantity:
- 50 uL
- Category:
- -
- Supplier:
- Abfron
- Gene target:
- Mouse polyclonal SPPL2a Host
Related genes to: Mouse polyclonal to SPPL2a, Host Mouse
- Gene:
- SPPL2A NIH gene
- Name:
- signal peptide peptidase like 2A
- Previous symbol:
- -
- Synonyms:
- IMP3, PSL2
- Chromosome:
- 15q21.2
- Locus Type:
- gene with protein product
- Date approved:
- 2012-02-21
- Date modifiied:
- 2014-11-19
Related products to: Mouse polyclonal to SPPL2a, Host Mouse
Related articles to: Mouse polyclonal to SPPL2a, Host Mouse
- The Alzheimer's disease (AD) brain is characterized by dysregulated expression of multiple microRNAs (miRNA), positioning them as promising diagnostic and therapeutic targets. The levels of glia-enriched miR-223 are abnormal in the brains and plasma of AD patients and miR-223 is neuroprotective in models of stroke. However, whether miR-223 can be beneficial in AD is not known. Here, we report that intracerebroventricular (ICV) injection of miR-223 oligonucleotide mimic alleviated cognitive impairment, reduced amyloid beta (Aβ) pathology, and ameliorated the defects in synaptic marker expression in App AD model mice. Mechanistically, miR-223 induced microglial clustering around Aβ plaques with a concomitant upregulation of microglial phagocytic receptors AXL, TREM2 and CD11c, while pharmacological microglial depletion abolished the plaque-clearance phenotype. Moreover, in human iPSC-derived microglia miR-223 directly targeted multiple genes in the endo-lysosomal pathway, including AD risk gene , indicating that it acts as a major regulator of microglial phenotype. Lastly, long-term AAV-mediated overexpression of miR-223 recapitulates its beneficial effects on cognition, pathology, and synaptic marker expression. Our study demonstrates a novel approach for the treatment of AD using miR-223 and highlights the potential of RNAi-based therapeutics in neurodegenerative disease. - Source: PubMed
Publication date: 2026/07/23
Krunic AndreGanesh Nikkitha UmeshCoskun UgurBrennan WilliamPatel ChandaniJoshi OjasiLee JaneGu Tori ShiyangCaruso JaclynO'Connell AoifeLisboa CharlesCrossland NicholasKurkela MargaretaTcw JuliaFowler AbigailTay Tuan LengFischer AndreDelalle IvanaBlusztajn Jan KMellott Tiffany J - The failure of γ-secretase inhibitors in clinical trials of Alzheimer's disease (AD) has shifted the focus toward more selective targets, specifically SPPL2a (signal peptide-peptidase-like 2a), which is emerging as a critical therapeutic target in AD because of its role in processing TMEM106B. While recent cryo-EM structures have provided essential static snapshots, the dynamic mechanisms governing substrate entry and inhibitor recognition remain unresolved. Here, we present the first microsecond-time scale, all-atom molecular dynamics characterization of human SPPL2a in its apo and inhibitor-bound states, alongside a comparative analysis of the γ-secretase catalytic subunit, PS1. Our simulations reveal that SPPL2a is highly dynamic and undergoes an inhibitor-induced disorder-to-order transition in the TM6a region, where the helicity increases from 10% to 77%. We characterized the lateral gate dynamics of TM2, revealing that inhibitor binding fundamentally remodels the interhelical contact network and quenches conformational sampling. Moreover, we identified a unique inhibitor-stabilized lipid hotspot at Trp189 and demonstrated that SPPL2a utilizes a distributed polar network for binding energy, in contrast to the concentrated aspartate-driven affinity of PS1. These findings provide a quantitative atomistic blueprint of SPPL2a dynamics, offering a structural basis that can be exploited for the design of selectivity-guided therapeutics to bypass the clinical failures associated with nonspecific intramembrane protease inhibition. - Source: PubMed
Dutta SagnikaSingh Mahender KumarDehury Budheswar - Crohn's disease (CD) is a chronic inflammatory bowel disease marked by immune imbalance and monocyte dysfunction. IFITM3, a palmitoylation-related immune protein, may play a role in this process, but its involvement in CD remains unclear. This study aimed to explore the causal role of IFITM3 and related proteins in CD using Mendelian randomization, multi-omics analysis, and machine learning, to identify potential diagnostic markers and therapeutic targets. - Source: PubMed
Publication date: 2026/06/04
Song XinxiaYuan TangyuXing JiayinLiu Pengtao - Mesenchymal spindle cell tumors represent a heterogeneous group of neoplasms defined by distinct clinicopathologic features and diverse molecular alterations. While USP6 rearrangements are well-established in nodular fasciitis and related entities, fusions involving other ubiquitin-specific proteases, such as USP2 and USP8 , have only recently emerged. Prompted by sporadic reports of USP8 fusions in matrix-rich neoplasms, we aimed to characterize the clinicopathologic and molecular spectrum of USP2/USP8-rearranged mesenchymal tumors. We retrospectively analyzed 19 tumors, evaluating clinical, histopathologic features, immunohistochemical profiles, whole-transcriptome RNA sequencing, and DNA methylation profiling. Nineteen tumors were identified, harboring either USP8 (n=12) or USP2 (n=7) fusions. The cohort included patients aged 3 to 70 years (median: 32). Tumors primarily affected the distal extremities, with the notable exception of 2 intracardiac cases in pediatric patients, harboring USP8 fusions ( CBLB :: USP8 and SPPL2A :: USP8 ). Histologically, all cases were composed of bland spindle cells arranged in either a myofibromatous or an inflammatory pattern; notably, USP2-fused tumors exhibited an exclusively myofibromatous morphology. Immunohistochemically, SMA was frequently expressed, while desmin, h-caldesmon, ALK, ROS1, panTRK, and CD34 were consistently negative. Transcriptomic analysis demonstrated proximity to myofibroma and nodular fasciitis profiles, rather than forming a distinct USP2/8-specific cluster. No cases showed malignant behavior or recurrence during the available follow-up period. USP2/8-rearranged neoplasms represent a morphologically diverse but biologically indolent subset of myofibroblastic tumors. They exhibit significant overlap with USP6-associated lesions and PDGFR-altered myofibromas. Recognizing these fusions is critical to avoid diagnostic pitfalls and overtreatment, particularly when they present in unusual sites, such as the heart. - Source: PubMed
Publication date: 2026/04/22
Frankel DianeMarsan-Fratini Anne-ClaireLe Loarer FrançoisBouvier CorinneMeurgey AlexandraBaltrès AlineHoulier AuréliePissaloux DanielEl Zein SophieWatson SarahGarcia JeremyGuillemot DelphinePierron GaëlleTirode FranckKaranian MarieMacagno Nicolas - Proteases represent a diverse family of enzymes that catalyze the hydrolysis of peptide bonds, modulating numerous biological processes. Among their substrates, CD74-also known as the invariant chain-has received increased research attention due to its multifunctional roles in both innate and adaptive immunity. This review provides an overview of current knowledge on protease-mediated interactions with CD74. The protein was originally identified as a chaperone for major histocompatibility complex class II (MHC-II) molecules. Proteolytic cleavage of CD74, most notably by cathepsin S, is essential for the release of MHC-II and the initiation of antigen presentation. However, CD74 has since emerged as a central regulator of processes extending well beyond antigen presentation. More recent findings reveal that CD74, acting as a receptor of macrophage migration inhibitory factor, also participates in signaling pathways in non-immune cells, independent of its classical chaperone function. Proteolytic processing of CD74 can trigger signaling cascades that modulate gene expression, underscoring its multifunctionality. Dysregulation of CD74 cleavage and its interaction with proteases has been linked to diverse pathological conditions, including cancer and autoimmune diseases, where aberrant protease activity disrupts CD74 function and promotes disease progression. - Source: PubMed
Publication date: 2025/12/10
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