Synphilin-1 represents a cytoplasmic protein that interacts with alpha-synuclein and localizes close to synaptic vesicles. The interaction of synphilin-1 with several proteins involved in Parkinson's disease suggests that it might be involved in the pathogenesis of the disease. Nonetheless, the function of synphilin-1 remains unclear. In the present study, we generated transgenic mice expressing human synphilin-1 under the prion protein promoter. Synphilin-1 was widely expressed in neurons in the brain including the substantia nigra, where massive loss of dopamine neurons was not observed. In the transgenic mouse brain, synphilin-1 protein was polyubiquitinated, and partially insoluble. Although modified-SHIRPA revealed no significant difference in behavior and morphology, the reduced rotarod performance and step length were observed in transgenic mice as compared with non-transgenic littermates. Synphilin-1 might be involved in motor function, and its accumulation in the central nervous system can cause motor impairments.
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http://dx.doi.org/10.1016/j.neulet.2008.08.073 | DOI Listing |
Sci Immunol
January 2025
Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
Chronic low-grade inflammation observed in older adults, termed inflammaging, is a common feature underlying a multitude of aging-associated maladies including a decline in hematopoietic activity. However, whether suppression of inflammaging can preserve hematopoietic health span remains unclear, in part because of a lack of tools to measure inflammaging within hematopoietic stem cells (HSCs). Here, we identify thrombospondin-1 (Thbs1) as an essential regulator of inflammaging within HSCs.
View Article and Find Full Text PDFSci Immunol
January 2025
Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
The NLRP3 inflammasome plays a critical role in innate immunity and inflammatory diseases. NIMA-related kinase 7 (NEK7) is essential for inflammasome activation, and its interaction with NLRP3 is enhanced by K efflux. However, the mechanism by which K efflux promotes this interaction remains unknown.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Laboratory of Obesity and Aging Research, Cardiovascular Branch, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892.
Mitochondrial endonuclease G (EndoG) contributes to chromosomal degradation when it is released from mitochondria during apoptosis. It is presumed to also have a mitochondrial function because EndoG deficiency causes mitochondrial dysfunction. However, the mechanism by which EndoG regulates mitochondrial function is not known.
View Article and Find Full Text PDFSci Adv
January 2025
Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Adipocyte lipolysis controls systemic energy levels and metabolic homeostasis. Lipolysis is regulated by posttranslational modifications of key lipolytic enzymes. However, less is known about the transcriptional mechanisms that regulate lipolysis.
View Article and Find Full Text PDFCalcif Tissue Int
January 2025
Jerry L. Pettis Memorial VA Medical Center, VA Loma Linda Healthcare System, Loma Linda, CA, USA.
This study assessed the feasibility of miR17 ~ 92-based antiresorptive strategy by determining the effects of conditional transgenic (cTG) overexpression of miR17 ~ 92 in myeloid cells on bone and osteoclasts. Osteoclasts of male and female cTG mutant mice each showed 3- to fivefold overexpression of miR17 ~ 92 cluster genes compared to those of age- and sex-matched wildtype (WT) littermates. Male but not female cTG mutant mice had more trabecular and cortical bones as well as lower bone resorption reflected by reduction in osteoclast number and resorbing surface.
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