Miniatura

Fitxers

bpa.12996.pdf (24.76 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2021-07-04

Llicència de publicació

cc by-nc-nd (c) Ferrer, Isidro (Ferrer Abizanda) et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/179131

Dysregulated protein phosphorylation: A determining condition in the continuum of brain aging and Alzheimer's disease

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1111/bpa.12996

Resum

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.

Matèries

Malaltia d'Alzheimer, Envelliment, Proteòmica, Cervell

Matèries (anglès)

Alzheimer's disease, Aging, Proteomics, Brain

Citació

Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

Citació

FERRER, Isidro (ferrer abizanda), ANDRÉS BENITO, Pol, AUSÍN, Karina, PAMPLONA, Reinald, RÍO FERNÁNDEZ, José antonio del, FERNÁNDEZ IRIGOYEN, Joaquín, SANTAMARÍA, Enrique. Dysregulated protein phosphorylation: A determining condition in the continuum of brain aging and Alzheimer's disease. _Brain Pathology_. 2021. Vol. 31, núm. 6, pàgs. e12996. [consulta: 16 de abril de 2026]. ISSN: 1750-3639. [Disponible a: https://hdl.handle.net/2445/179131]

Exportar metadades

JSON - METS

Compartir registre