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TMEM106B C-terminal fragments aggregate and drive neurodegenerative proteinopathy.
bioRxiv
June 2024
Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Genetic variation in the lysosomal and transmembrane protein 106B (TMEM106B) modifies risk for a diverse range of neurodegenerative disorders, especially frontotemporal lobar degeneration (FTLD) with progranulin (PGRN) haplo-insufficiency, although the molecular mechanisms involved are not yet understood. Through advances in cryo-electron microscopy (cryo-EM), homotypic aggregates of the C-Terminal domain of TMEM106B (TMEM CT) were discovered as a previously unidentified cytosolic proteinopathy in the brains of FTLD, Alzheimer's disease, progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB) patients. While it remains unknown what role TMEM CT aggregation plays in neuronal loss, its presence across a range of aging related dementia disorders indicates involvement in multi-proteinopathy driven neurodegeneration.
View Article and Find Full Text PDFTransmembrane proteins with unknown function (TMEMs) as ion channels: electrophysiological properties, structure, and pathophysiological roles.
Exp Mol Med
April 2024
Center for Cognition and Sociality, Life Science Cluster, Institute for Basic Science (IBS), 55 Expo-ro, Yuseong-gu, Daejeon, 34126, Republic of Korea.
A transmembrane (TMEM) protein with an unknown function is a type of membrane-spanning protein expressed in the plasma membrane or the membranes of intracellular organelles. Recently, several TMEM proteins have been identified as functional ion channels. The structures and functions of these proteins have been extensively studied over the last two decades, starting with TMEM16A (ANO1).
View Article and Find Full Text PDFSingle-cell atlas of healthy human blood unveils age-related loss of NKG2CGZMBCD8 memory T cells and accumulation of type 2 memory T cells.
Immunity
December 2023
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address:
Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25-85 years old. From this, we generated a dataset from ∼2 million cells that described 55 subpopulations of blood immune cells.
View Article and Find Full Text PDFBreast cancer is the most commonly diagnosed malignancy and the major leading cause of tumor-related deaths in women. It is estimated that the majority of breast tumor-related deaths are a consequence of metastasis, to which no cure exists at present. The FAK family proteins Proline-rich tyrosine kinase (PYK2) and focal adhesion kinase (FAK) are highly expressed in breast cancer, but the exact cellular and signaling mechanisms by which they regulate tumor cell invasiveness and consequent metastatic dissemination are mostly unknown.
View Article and Find Full Text PDFTMEM44 as a Novel Prognostic Marker for Kidney Renal Clear Cell Carcinoma is Associated with Tumor Invasion, Migration and Immune Infiltration.
Biochem Genet
April 2024
Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Transmembrane (TMEM) proteins are integral membrane proteins that traverse biological membranes. Several members of the TMEM family have been linked to the development and progression of various tumors. However, the specific role and mechanism of TMEM44 in tumor biology remain largely unexplored.
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