Proteostatic modulation in brain aging without associated Alzheimer's disease-and age-related neuropathological changes
Fecha
2023Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Identificador del proyecto
Impacto
|
10.18632/aging.204698
Resumen
Aims: (Phospho)proteomics of old-aged subjects without cognitive or behavioral symptoms, and without ADneuropathological 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 SWA ...
[++]
Aims: (Phospho)proteomics of old-aged subjects without cognitive or behavioral symptoms, and without ADneuropathological 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. [--]
Materias
(Phospho)Proteomics,
Brain aging,
Cytoskeleton,
Kinases,
Membranes,
Mitochondria,
Proteome,
Synapsis
Editor
Impact Journals
Publicado en
Aging, 15(9) 3295-3330
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
The project leading to these results received funding from
the “la Caixa” Foundation (ID 100010434) under the
agreement LCF/PR/HR19/52160007, HR18-00452 to IF
and JAdR. We thank CERCA Programme/Generalitat de
Catalunya for institutional support. The Proteomics
Platform of Navarrabiomed is a member of Proteored
(PRB3-ISCIII) and is supported by grant PT17/0019/009
to JFI, of the PE I+D+I 2013–2016 funded by ISCIII and
FEDER. Parts of this work were funded by a grant from
the Spanish Ministry of Science Innovation and
Universities (Ref. PID2019-110356RB-I00) to JFI and
ES, and the Department of Economic and Business Development of the Government of Navarra (Ref. 0011-
1411-2020-000028) to ES.
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La licencia del ítem se describe como © 2023 Andrés-Benito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.