B lymphocytes and T lymphocytes utilize several proteins with common functions to transduce signals from their respective receptors. However, at the hierarchial signalling level of SLP-76 [Src homology 2(SH2) domain-containing leukocyte protein of 76-kDa] and LAT (linker for activation of T cells) in T cells, the only corresponding protein in B cells was known to be BLNK (B cell linker protein). It was thought that perhaps BLNK performed the cognate roles of SLP-76 and LAT in B cells; however, mounting evidence to the contrary revealed that this hypothesis was not robust. Two laboratories have recently described the characterization of a protein expressed in B cells and myeloid cells, alternatively termed NTAL (non-T cell activation linker) or LAB (linker for activation of B cells). NTAL/LAB and LAT may have arisen from a primordial gene-duplicating event, but genes that code for the two proteins do not share a very high degree of sequence identity. Wange discusses the results of the two reports, the evidence for functional homology between LAT and NTAL/LAB, and the possibility that the differences between them might lead to specific clinical therapeutics to manipulate immune cell responses.
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http://dx.doi.org/10.1124/mi.3.2.75 | DOI Listing |
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December 2024
Department of Pharmaceutics, School of Pharmacy, Air Force Medical University, Xi'an, 710032, China.
Mitochondrial dysfunction plays an important role in neuroinflammation and cognitive impairment in Alzheimer's disease (AD). Herein, this work designs a mitochondria-targeted micelle CsA-TK-SS-31 (CTS) to block the progression of AD by simultaneously alleviating mitochondrial dysfunction in microglia and neurons. The mitochondria-targeted peptide SS-31 drives cyclosporin A (CsA) to penetrate the blood-brain barrier (BBB) and delivers CsA to mitochondria of microglia and neurons in the brains of 5 × FAD mice.
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December 2024
Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India. Electronic address:
Matrix metalloproteases (MMPs) are the proteolytic enzymes accountable for extracellular matrix (ECM) modification through their Zn-dependent catalytic activity. Among these, MMP-12 is one of the crucial MMPs that contributes to various disease states including different types of cancers and other major pathophysiological conditions including COPD, asthma, emphysema, skin diseases, arthritis, vascular diseases, and neurological disorders. The majority of the MMP-12 inhibitors should have three constitutional pharmacophoric features (i.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2024
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. Electronic address:
Tissue transglutaminase (TG2) is a multifunctional protein that can catalyze the cross-linking between proteins, and function as a G-protein. TG2's unregulated behaviour has been associated with fibrosis, celiac disease and cancer metastasis. Recently, small molecule irreversible inhibitors have been designed, bearing an electrophilic warhead that can react with the catalytic cysteine, abolishing TG2's catalytic and G-protein capabilities.
View Article and Find Full Text PDFInt J Pharm
December 2024
Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork T12 YN60, Ireland; Department of Haematology and Cancer Research@UCC, Cork University Hospital, University College Cork, Cork T12 XF62, Ireland. Electronic address:
The presence of multiple hydroxyl groups, at positions C2, C3 and C6 on the cyclodextrin (CD) ring structure allows for extensive functionalisation, enabling the development of biomaterials with significant potential for therapeutic siRNA delivery. To identify structural modifications that enhance activity, a range of cationic amphiphilic CDs, including both β- and γ-CDs, were synthesised, compared and evaluated. Each CDs incorporated a C lipid chain on the primary face of the CD.
View Article and Find Full Text PDFBioorg Chem
December 2024
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education and School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address:
Protein Arginine Methyltransferase 5 (PRMT5) is an important player in breast cancer cell activity, and innovative fluorescent ligands targeting this enzyme offer revolutionary, real-time insights into its role in cancer progression, unlocking new avenues for diagnosis and treatment. This study introduces fluorescence-labeled PRMT5 ligands, highlighting their applications in visualizing PRMT5, monitoring enzymatic activity as well as studying toxicity. Herein, we describe the design, synthesis, and cellular imaging of a series of fluorescent ligands that target PRMT5.
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