Size of membrane microparticles (MPs) from blood plasma and MPs produced in vitro by activated endothelial cells (ECs), monocytes, THP-1 monocytic cells, granulocytes, and platelets was evaluated by dynamic light scattering. MPs were sedimented from the culture media, cell supernatants, and plasma at 20 000 g for 30 min. Average diameters of all types of MPs ranged from 300 to 600 nm. Plasma MPs had the smallest size. Close sizes were registered for MPs from platelets and THP-1 cells. MPs from monocytes were larger, and MPs from granulocytes and ECs were the largest ones. The data obtained indicate that the size of membrane MPs depends on the type of their cell-producers.
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http://dx.doi.org/10.1134/S1607672916050045 | DOI Listing |
Sci Adv
January 2025
Department of Biochemistry Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Lysosomal pH dysregulation is a critical element of the pathophysiology of neurodegenerative diseases, cancers, and lysosomal storage disorders (LSDs). To study the role of lysosomes in pathophysiology, probes to analyze lysosomal size, positioning, and pH are indispensable tools. Here, we developed and characterized a ratiometric genetically encoded lysosomal pH probe, RpH-ILV, targeted to a subpopulation of lysosomal intraluminal vesicles.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Background: The brain is shielded from the peripheral circulation by central nervous system (CNS) barriers, comprising the well-known blood-brain barrier (BBB) and the less recognized blood-cerebrospinal fluid (CSF) barrier located within the brain ventricles. The gut microbiota represents a diverse and dynamic population of microorganisms that can influence the health of the host, including the development of neurological disorders like Alzheimer's disease (AD). However, the intricate mechanisms governing the interplay between the gut and brain remain elusive, and the means by which gut-derived signals traverse the CNS barriers remain unclear.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Background: Common and rare variants in SORL1 have been associated with increased risk of Alzheimer's disease (AD). Since 2019, we have run an international collaborative research initiative to ascertain a Peruvian cohort for Alzheimer's disease and other related dementias for genetic studies (PeADI).
Method: A Peruvian family (4 AD cases and two mild cognitive impairment (MCI) cases) was recruited through the PeADI study.
Alzheimers Dement
December 2024
University of Washington, Seattle, WA, USA.
Background: The SORL1 gene (SORLA) is strongly associated with risk of developing Alzheimer's disease (AD). SORLA is a regulator of endosomal trafficking in neurons and interacts with retromer, a complex that is a "master conductor" of endosomal trafficking. Because of its size, SORLA is difficult to target therapeutically.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Columbia University, New York, NY, USA.
Background: We examined AD-associated loci to demonstrate how the new FunGen-xQTL resource reveals new insights into the sequence of events leading from health to the amyloid and tau proteinopathies that define AD, as well as subsequent cognitive decline.
Method: We utilized FunGen-xQTL resources (including cell subtype-specific eQTL results) to deconstruct the genetic regulation and cellular specificity of AD loci. Using transcriptomic and proteomic data systematically derived from iPSC-derived neurons and astrocytes in up to 48 iPSC lines we highlight and further dissect those genetic effects that replicate in the proper induced iPSC-derived neuron (iN) or astrocyte (iAstro) model system.
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