We found previously that aggregated insoluble tau protein in progressive supranuclear palsy (PSP) brains exhibits a heterogeneous pattern that is not segregated by the type of clinical presentation. Here we have investigated tau isoform composition from 20 PSP cases and found marked variation between different brains. Cases were classified into three groups, each comprising essentially of (1) 1N4R; (2) 1N4R and 1N3R; or (3) 1N4R, 1N3R and 0N4R tau isoforms. There was also an absence of a simple relationship between isoform composition and the pattern of insoluble tau before dephosphorylation. We conclude that there is distinct molecular heterogeneity in the involvement of tau isoforms in the tau pathology in PSP.
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http://dx.doi.org/10.1016/j.molbrainres.2003.11.007 | DOI Listing |
Biomedicines
December 2024
Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Preeclampsia (preE) is a severe multisystem hypertensive syndrome of pregnancy associated with ischemia/hypoxia, angiogenic imbalance, apolipoprotein E (ApoE)-mediated dyslipidemia, placental insufficiency, and inflammation at the maternal-fetal interface. Our recent data further suggest that preE is associated with impaired autophagy, vascular dysfunction, and proteinopathy/tauopathy disorder, similar to neurodegenerative diseases such as Alzheimer's disease (AD), including the presence of the cis stereo-isoform of phosphorylated tau (cis P-tau), amyloid-β, and transthyretin in the placenta and circulation. This review provides an overview of the factors that may lead to the induction and accumulation of cis P-tau-like proteins by focusing on the inactivation of peptidyl-prolyl cis-trans isomerase (Pin1) that catalyzes the cis to trans isomerization of P-tau.
View Article and Find Full Text PDFJ Neurochem
January 2025
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA.
A hallmark of Alzheimer disease (AD) and tauopathies, severe neurodegenerative diseases, is the progressive aggregation of Tau, also known as microtubule-associated Tau protein. Full-length Tau, also known as 2N4R, contains two N-terminal inserts that bind to tubulin. This facilitates the self-assembly of tubulin simultaneously enhancing stability of cell microtubules.
View Article and Find Full Text PDFAlzheimers Res Ther
January 2025
Section of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, 214-28, Sweden.
We have previously demonstrated that the intracellular, non-GPI anchored CD59 isoforms IRIS-1 and IRIS-2 (Isoforms Rescuing Insulin Secretion 1 and 2) are necessary for insulin secretion from pancreatic β-cells. While investigating their expression across human tissues, we identified IRIS-1 and IRIS-2 mRNA in the human brain, though their protein expression and function remained unclear. This study shows the presence of both IRIS-1 and 2 proteins in the human brain, specifically in neurons and astrocytes.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Research Center for Accelerator and Radioisotope Science, Tohoku University, Sendai, Miyagi 980-0845, Japan.
Alzheimer's disease (AD) and non-AD tauopathies are dominant public health issues driven by several factors, especially in the aging population. The discovery of first-generation radiotracers, including [F]FDDNP, [C]PBB3, [F]flortaucipir, and the [F]THK series, for the in vivo detection of tauopathies has marked a significant breakthrough in the fields of neuroscience and radiopharmaceuticals, creating a robust new category of labeled compounds: tau positron emission tomography (PET) tracers. Subsequently, other tau PET tracers with improved binding properties have been developed using various chemical scaffolds to target the three-repeat/four-repeat (3R/4R) tau folds in AD.
View Article and Find Full Text PDFAlzheimers Res Ther
January 2025
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA.
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