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Proteostatic Modulation in Brain Aging Without Associated Alzheimer's



May 18, 2023

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  • Aging-US published this trending research paper on May 13, 2023, in Volume 15, Issue 9, entitled, “Proteostatic modulation in brain aging without associated Alzheimer’s disease-and age-related neuropathological changes" by researchers from Neurologic Diseases and Neurogenetics Group - Bellvitge Institute for Biomedical Research (IDIBE LL), L’Hospitalet de Llobregat, Barcelona 08907, Spain; CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, L’Hospitalet de Llobregat, Barcelona 08907, Spain; Clinical Neuroproteomics Unit, Proteomics Platform, Proteored-ISCIII, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), diSNA, Pamplona 31008, Spain; Neuropathology Group, Institute of Biomedical Research, IDIBELL, L’Hospitalet de Llobregat, Barcelona 08907, Spain; Molecular and Cellular Neurobiotechnology Group, Institute of Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology, Science Park Barcelona (PCB), Barcelona 08028, Spain; Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08007, Spain; Department of Pathology and Experimental Therapeutics, University of Barcelona, L’Hospitalet de Llobregat, Barcelona 08907, Spain. DOI - Corresponding authors - Isidro Ferrer -, and Pol Andrés-Benito - Abstract Aims: (Phospho)proteomics of old-aged subjects without cognitive or behavioral symptoms, and without AD-neuropathological changes and lacking any other neurodegenerative alteration will increase understanding about the physiological state of human brain aging without associate neurological deficits and neuropathological lesions. Methods: (Phospho)proteomics using conventional label-free- and SWATH-MS (Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) has been assessed in the frontal cortex (FC) of individuals without NFTs, senile plaques (SPs) and age-related co-morbidities classified by age (years) in four groups; group 1 (young, 30–44); group 2 (middle-aged: MA, 45-52); group 3 (early-elderly, 64–70); and group 4 (late-elderly, 75–85). Results: Protein levels and deregulated protein phosphorylation linked to similar biological terms/functions, but involving different individual proteins, are found in FC with age. The modified expression occurs in cytoskeleton proteins, membranes, synapses, vesicles, myelin, membrane transport and ion channels, DNA and RNA metabolism, ubiquitin-proteasome-system (UPS), kinases and phosphatases, fatty acid metabolism, and mitochondria. Dysregulated phosphoproteins are associated with the cytoskeleton, including microfilaments, actin-binding proteins, intermediate filaments of neurons and glial cells, and microtubules; membrane proteins, synapses, and dense core vesicles; kinases and phosphatases; proteins linked to DNA and RNA; members of the UPS; GTPase regulation; inflammation; and lipid metabolism. Noteworthy, protein levels of large clusters of hierarchically-related protein expression levels are stable until 70. However, protein levels of components of cell membranes, vesicles and synapses, RNA modulation, and cellular structures (including tau and tubulin filaments) are markedly altered from the age of 75. Similarly, marked modifications occur in the larger phosphoprotein clusters involving cytoskeleton and neuronal structures, membrane stabilization, and kinase regulation in the late elderly. Conclusions: Present findings may increase understanding of human brain proteostasis modifications in the elderly in the subpopulation of individuals not having AD neuropathological change and any other neurodegenerative change in any telencephalon region. Keywords - aging, brain aging, cytoskeleton, membranes, synapsis, mitochondria, kinases, (phospho)proteomics, proteome About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ and connect with us: SoundCloud - Facebook - Twitter - Instagram - YouTube - LinkedIn - Pinterest - MEDIA@IMPACTJOURNALS.COM

    Analytical TechniquesMolecular BiologyNeuroscience

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