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Neuronal CD59 isoforms IRIS-1 and IRIS-2 as regulators of neurotransmitter release with implications for Alzheimer's disease.
Alzheimers 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 PDFExploring the Role of Variants in Italian ALS Patients.
Genes (Basel)
December 2024
Centro Clinico NeMO Adulti, Fondazione Serena Onlus-Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
Variants in Cyclin F () have been associated to amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) in a group of cases. The objectives of this study were to determine the contribution of in a large cohort of Italian ALS patients, to look for genotype-phenotype correlation of the mutations and to evaluate the -associated clinical features. We applied next-generation sequencing technologies on 971 unrelated Italian ALS patients and we filtered results to look for variants in gene.
View Article and Find Full Text PDFTherapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer's Amyloidosis.
Nutrients
December 2024
Grupo de Neuropsicofarmacología, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Unidades Clínicas de Neurología y Salud Mental, 29010 Málaga, Spain.
Background/objectives: Alzheimer's disease (AD), a leading cause of dementia, lacks effective long-term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Aβ) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut.
View Article and Find Full Text PDFRoscovitine, a CDK Inhibitor, Reduced Neuronal Toxicity of mHTT by Targeting HTT Phosphorylation at S1181 and S1201 In Vitro.
Int J Mol Sci
November 2024
Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Article Synopsis
- * Research has focused on post-translational modifications of the HTT protein, with findings showing that certain modifications can reduce the toxicity of the mutant protein in cell and animal models.
- * A study identified cyclin-dependent kinases (CDKs) that influence the phosphorylation of specific serine sites on HTT, and the CDK inhibitor roscovitine demonstrated protective effects against mutant HTT toxicity in HD mice, highlighting its potential as a pre-clinical therapeutic.
Palmitoyl-L-carnitine induces tau phosphorylation and mitochondrial dysfunction in neuronal cells.
PLoS One
November 2024
Division of Brain Disease Research, Department for Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju-si, Chungcheongbuk-do, Republic of Korea.
Alzheimer's disease (AD) is characterized by cognitive decline and memory loss, involving mechanisms such as tau hyperphosphorylation and mitochondrial dysfunction. Increasing evidence suggests that age-related alterations in metabolite levels are crucial for the pathogenesis of AD. Here, we analyzed serum metabolites from mice of various ages (2, 4, 14, and 21 months old) using mass spectrometry.
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