Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/179131
Title: Dysregulated protein phosphorylation: A determining condition in the continuum of brain aging and Alzheimer's disease
Author: Ferrer, Isidro (Ferrer Abizanda)
Andrés Benito, Pol
Ausín, Karina
Pamplona, Reinald
Rio, José Antonio del
Fernández Irigoyen, Joaquín
Santamaría, Enrique
Keywords: Malaltia d'Alzheimer
Envelliment
Proteòmica
Cervell
Alzheimer's disease
Aging
Proteomics
Brain
Issue Date: 4-Jul-2021
Publisher: Wiley
Abstract: Tau hyperphosphorylation is the first step of neurofibrillary tangle (NFT) formation. In the present study, samples of the entorhinal cortex (EC) and frontal cortex area 8 (FC) of cases with NFT pathology classified as stages I-II, III-IV, and V-VI without comorbidities, and of middle-aged (MA) individuals with no NFT pathology, were analyzed by conventional label-free and SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) to assess the (phospho)proteomes. The total number of identified dysregulated phosphoproteins was 214 in the EC, 65 of which were dysregulated at the first stages (I-II) of NFT pathology; 167 phosphoproteins were dysregulated in the FC, 81 of them at stages I-II of NFT pathology. A large percentage of dysregulated phosphoproteins were identified in the two regions and at different stages of NFT progression. The main group of dysregulated phosphoproteins was made up of components of the membranes, cytoskeleton, synapses, proteins linked to membrane transport and ion channels, and kinases. The present results show abnormal phosphorylation of proteins at the first stages of NFT pathology in the elderly (in individuals clinically considered representative of normal aging) and sporadic Alzheimer's disease (sAD). Dysregulated protein phosphorylation in the FC precedes the formation of NFTs and SPs. The most active period of dysregulated phosphorylation is at stages III-IV when a subpopulation of individuals might be clinically categorized as suffering from mild cognitive impairment which is a preceding determinant stage in the progression to dementia. Altered phosphorylation of selected proteins, carried out by activation of several kinases, may alter membrane and cytoskeletal functions, among them synaptic transmission and membrane/cytoskeleton signaling. Besides their implications in sAD, the present observations suggest a molecular substrate for "benign" cognitive deterioration in "normal" brain aging.
Note: Reproducció del document publicat a: https://doi.org/10.1111/bpa.12996
It is part of: Brain Pathology, 2021, num. e12996
URI: http://hdl.handle.net/2445/179131
Related resource: https://doi.org/10.1111/bpa.12996
ISSN: 1750-3639
Appears in Collections:Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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