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Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
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File: /var/www/html/index.php
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Severity: Warning
Message: Trying to access array offset on value of type null
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File: /var/www/html/application/controllers/Detail.php
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Tauopathies, including Alzheimer's disease (AD) and frontotemporal lobar degeneration with Tau pathology (FTLD-tau), are a group of neurodegenerative disorders characterized by Tau hyperphosphorylation. Post-translational modifications of Tau such as phosphorylation and truncation have been demonstrated to be an essential step in the molecular pathogenesis of these tauopathies. In this work, we demonstrate the existence of a new, human-specific truncated form of Tau generated by intron 12 retention in human neuroblastoma cells and, to a higher extent, in human RNA brain samples, using qPCR and further confirming the results on a larger database of human RNA-seq samples. Diminished protein levels of this new Tau isoform are found by Westernblotting in Alzheimer's patients' brains (Braak I n = 3; Braak II n = 6, Braak III n = 3, Braak IV n = 1, and Braak V n = 10, Braak VI n = 8) with respect to non-demented control subjects (n = 9), suggesting that the lack of this truncated isoform may play an important role in the pathology. This new Tau isoform exhibits similar post-transcriptional modifications by phosphorylation and affinity for microtubule binding, but more interestingly, is less prone to aggregate than other Tau isoforms. Finally, we present evidence suggesting this new Tau isoform could be linked to the inhibition of GSK3β, which would mediate intron 12 retention by modulating the serine/arginine rich splicing factor 2 (SRSF2). Our results show the existence of an important new isoform of Tau and suggest that further research on this less aggregation-prone Tau may help to develop future therapies for Alzheimer's disease and other tauopathies.
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http://dx.doi.org/10.1007/s00401-021-02317-z | DOI Listing |
Expert Opin Ther Pat
December 2024
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Introduction: Neuroinflammation is correlated to neurodegenerative diseases like Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington Disease (HD) and Parkinson's disease (PD). A lot of recent research and patents are focused on the design and synthesis of arachidonic acid Lipoxygenase (ALOX) inhibitors for the treatment of neurodegenerative diseases.
Areas Covered: The survey covers natural products, synthesis, hybrids, and assessments of biological effects in biological studies as ALOX inhibitors.
Front Immunol
December 2024
Department of Otolaryngology, The Second Affiliated Hospital of the Army Military Medical University, Chongqing, China.
MS4A (membrane-spanning 4-domain, subfamily A) molecules are categorized into tetraspanins, which possess four-transmembrane structures. To date, eighteen MS4A members have been identified in humans, whereas twenty-three different molecules have been identified in mice. MS4A proteins are selectively expressed on the surfaces of various immune cells, such as B cells (MS4A1), mast cells (MS4A2), macrophages (MS4A4A), Foxp3CD4 regulatory T cells (MS4A4B), and type 3 innate lymphoid cells (TMEM176A and TMEM176B).
View Article and Find Full Text PDFJ Biomed Opt
December 2024
University of Michigan, Department of Biomedical Engineering, Ann Arbor, Michigan, United States.
Significance: Alzheimer's disease (AD) is a predominant form of dementia that can lead to a decline in the quality of life and mortality. The understanding of the pathological changes requires monitoring of multiple cerebral biomarkers simultaneously with high resolution. Photoacoustic microscopy resolves single capillaries, allowing investigations into the most affected types of vessels.
View Article and Find Full Text PDFFront Neurosci
December 2024
Memory and Brain Wellness Center, University of Washington, Seattle, WA, United States.
Background: Alzheimer's disease (AD) is characterized by cerebral amyloid plaques and neurofibrillary tangles and disruption of large-scale brain networks (LSBNs). Transcranial magnetic stimulation (TMS) has emerged as a potential non-invasive AD treatment that may serve as an adjunct therapy with FDA approved medications.
Methods: We conducted a 10-subject open label, single site study evaluating the effect of functional connectivity-resting state functional MRI guided-approach to TMS targeting with dysfunctional LSBNs in subjects with biomarker-confirmed early-stage AD (https://clinicaltrials.
Beilstein J Nanotechnol
December 2024
Department of Immunology, Microbiology and Parasitology. Biological and Natural Sciences Institute. Federal University of Triângulo Mineiro. Uberaba, Minas Gerais, Brazil.
Biomimetic nanocarriers, engineered to mimic the characteristics of native cells, offer a revolutionary approach in the treatment of various complex human diseases. This strategy enhances drug delivery by leveraging the innate properties of cellular components, thereby improving biocompatibility and targeting specificity. Biomimetic nanocarriers demonstrate significant advancements in drug delivery systems against cancer therapy, Alzheimer's disease, autoimmune diseases, and viral infections such as COVID-19.
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