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1.
001-es BibID:
BIBFORM082384
035-os BibID:
(cikkazonosító)104509 (WoS)000481565000014 (Scopus)85067554418
Első szerző:
Mendonça, Clarissa Ferolla
Cím:
Proteomic signatures of brain regions affected by tau pathology in early and late stages of Alzheimer's disease / Clarissa Ferolla Mendonça, Magdalena Kuras, Fábio César Sousa Nogueira, Indira Plá, Tibor Hortobágyi, László Csiba, Miklós Palkovits, Éva Renner, Péter Döme, György Marko-Varga, Gilberto B. Domont, Melinda Rezeli
Dátum:
2019
ISSN:
0969-9961
Megjegyzések:
Background Alzheimer's disease (AD) is the most common neurodegenerative disorder. Depositions of amyloid β peptide (Aβ) and tau protein are among the major pathological hallmarks of AD. Aβ and tau burden follows predictable spatial patterns during the progression of AD. Nevertheless, it remains obscure why certain brain regions are more vulnerable than others; to investigate this and dysregulated pathways during AD progression, a mass spectrometry-based proteomics study was performed. Methods In total 103 tissue samples from regions early (entorhinal and parahippocampal cortices - medial temporal lobe (MTL)) and late affected (temporal and frontal cortices - neocortex) by tau pathology were subjected to label-free quantitative proteomics analysis. Results Considering dysregulated proteins during AD progression, the majority (625 out of 737 proteins) was region specific, while some proteins were shared between regions (101 proteins altered in two areas and 11 proteins altered in three areas). Analogously, many dysregulated pathways during disease progression were exclusive to certain regions, but a few pathways altered in two or more areas. Changes in protein expression indicate that synapse loss occurred in all analyzed regions, while translation dysregulation was preponderant in entorhinal, parahippocampal and frontal cortices. Oxidative phosphorylation impairment was prominent in MTL. Differential proteomic analysis of brain areas in health state (controls) showed higher metabolism and increased expression of AD-related proteins in the MTL compared to the neocortex. In addition, several proteins that differentiate brain regions in control tissue were dysregulated in AD. Conclusions This work provides the comparison of proteomic changes in brain regions affected by tau pathology at different stages of AD. Although we identified commonly regulated proteins and pathways during disease advancement, we found that the dysregulated processes are predominantly region specific. In addition, a distinct proteomic signature was found between MTL and neocortex in healthy subjects that might be related to AD vulnerability. These findings highlight the need for investigating AD's cascade of events throughout the whole brain and studies spanning more brain areas are required to better understand AD etiology and region vulnerability to disease.
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Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:
Neurobiology of Disease. - 130 (2019), p. 1-19. -
További szerzők:
Kuras, Magdalena
Nogueira, Fábio César Sousa
Plá, Indira
Hortobágyi Tibor (1965-) (patológus)
Csiba László (1952-) (neurológus, pszichiáter)
Palkovits Miklós
Renner Éva
Döme Péter
Marko-Varga György
Domont, Gilberto B.
Rezeli, Melinda
Pályázati támogatás:
2017-1.2.1-NKP-2017-00002
Egyéb
Internet cím:
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DOI
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Saját polcon:
2.
001-es BibID:
BIBFORM099463
035-os BibID:
(cikkazonosító)750665 (WoS)000713446000001 (Scopus)85118795095
Első szerző:
Velásquez, Erika
Cím:
Topological Dissection of Proteomic Changes Linked to the Limbic Stage of Alzheimer's Disease / Erika Velásquez, Beáta Szeitz, Jeovanis Gil, Jimmy Rodriguez, Miklós Palkovits, Éva Renner, Tibor Hortobágyi, Péter Döme, Fábio CS. Nogueira, György Marko-Varga, Gilberto B. Domont, Melinda Rezeli
Dátum:
2021
ISSN:
1664-3224
Megjegyzések:
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia worldwide. In AD, neurodegeneration spreads throughout different areas of the central nervous system (CNS) in a gradual and predictable pattern, causing progressive memory decline and cognitive impairment. Deposition of neurofibrillary tangles (NFTs) in specific CNS regions correlates with the severity of AD and constitutes the basis for disease classification into different Braak stages (I-VI). Early clinical symptoms are typically associated with stages III-IV (i.e., limbic stages) when the involvement of the hippocampus begins. Histopathological changes in AD have been linked to brain proteome alterations, including aberrant posttranslational modifications (PTMs) such as the hyperphosphorylation of Tau. Most proteomic studies to date have focused on AD progression across different stages of the disease, by targeting one specific brain area at a time. However, in AD vulnerable regions, stage-specific proteomic alterations, including changes in PTM status occur in parallel and remain poorly characterized. Here, we conducted proteomic, phosphoproteomic, and acetylomic analyses of human postmortem tissue samples from AD (Braak stage III-IV, n=11) and control brains (n=12), covering all anatomical areas affected during the limbic stage of the disease (total hippocampus, CA1, entorhinal and perirhinal cortices). Overall, ~6000 proteins, ~9000 unique phosphopeptides and 221 acetylated peptides were accurately quantified across all tissues. Our results reveal significant proteome changes in AD brains compared to controls. Among others, we have observed the dysregulation of pathways related to the adaptive and innate immune responses, including several altered antimicrobial peptides (AMPs). Notably, some of these changes were restricted to specific anatomical areas, while others altered according to disease progression across the regions studied. Our data highlights the molecular heterogeneity of AD and the relevance of neuroinflammation as a major player in AD pathology. Data are available via ProteomeXchange with identifier PXD027173.
Tárgyszavak:
Orvostudományok
Klinikai orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:
Frontiers in Immunology. - 12 (2021), p. 1-17. -
További szerzők:
Szeitz Beáta
Gil, Jeovanis
Rodriguez, Jimmy
Palkovits Miklós
Renner Éva
Hortobágyi Tibor (1965-) (patológus)
Döme Péter
Nogueira, Fábio César Sousa
Marko-Varga György
Domont, Gilberto B.
Rezeli, Melinda
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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