Bioinformatic analysis of the SPs and NFTs proteomes unravel putative biomarker candidates for Alzheimer's disease.

Autor: Ferreira MJC; Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal., Soares Martins T; Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal., Alves SR; Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal., Rosa IM; Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal., Vogelgsang J; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August University, Goettingen, Germany.; Translational Neuroscience Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA., Hansen N; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August University, Goettingen, Germany., Wiltfang J; Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal.; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August University, Goettingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany., da Cruz E Silva OAB; Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal., Vitorino R; Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal., Henriques AG; Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal.
Jazyk: angličtina
Zdroj: Proteomics [Proteomics] 2023 Aug; Vol. 23 (15), pp. e2200515. Date of Electronic Publication: 2023 May 01.
DOI: 10.1002/pmic.202200515
Abstrakt: Aging is the main risk factor for the appearance of age-related neurodegenerative diseases, including Alzheimer's disease (AD). AD is the most common form of dementia, characterized by the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs), the main histopathological hallmarks in AD brains. The core of these deposits are predominantly amyloid fibrils in SPs and hyperphosphorylated Tau protein in NFTs, but other molecular components can be found associated with these pathological lesions. Herein, an extensive literature review was carried out to obtain the SPs and NFTs proteomes, followed by a bioinformatic analysis and further putative biomarker validation. For SPs, 857 proteins were recovered, and, for NFTs, 627 proteins of which 375 occur in both groups and represent the common proteome. Gene Ontology (GO) enrichment analysis permitted the identification of biological processes and the molecular functions most associated with these lesions. Analysis of the SPs and NFTs common proteins unraveled pathways and molecular targets linking both histopathological events. Further, validation of a putative phosphotarget arising from the in silico analysis was performed in serum-derived extracellular vesicles from AD patients. This bioinformatic approach contributed to the identification of putative molecular targets, valuable for AD diagnostic or therapeutic intervention.
(© 2023 The Authors. Proteomics published by Wiley-VCH GmbH.)
Databáze: MEDLINE