Exploring the brain tissue proteome of TgCRND8 Alzheimer's Disease model mice under B vitamin deficient diet induced hyperhomocysteinemia by LC-MS top-down platform

Daniela Delfino, Diana Valeria Rossetti, Claudia Martelli, Ilaria Inserra, Federica Vincenzoni, Massimo Castagnola, Andrea Urbani, Sigfrido Scarpa, Andrea Fuso, Rosaria A. Cavallaro, Claudia Desiderio

Research output: Contribution to journalArticle

Abstract

The multifactorial nature of Late Onset Alzheimer's Disease (LOAD), the AD form of major relevance on epidemiological and social aspects, has driven the original investigation by LC-MS and top-down proteomics approach of the protein repertoire of the brain tissue of TgCRND8 model mice fed with a diet deficient in B vitamins. The analysis of the acid-soluble fraction of brain tissue homogenates identified a list of proteins and peptides, proteoforms and PTMs. In order to disclose possible modulations, their relative quantification in wild type and AD model mice under both B vitamin deficient and control diets was performed. The levels of metallothionein III, guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 and brain acid soluble protein 1 showed statistically significant alterations depending on genotype, diet or both effects, respectively. Particularly, metallothionein III exhibited increased levels in TgCRND8 mice under B vitamin deficient diet with respect to wild type mice under both diets. Brain acid soluble protein 1 showed the opposite, revealing decreased levels in all diet groups of AD model mice with respect to wild type mice in control diet. Lower levels of brain acid soluble protein 1 were also observed in wild type mice under deficiency of B vitamins. These results, besides contributing to increase the knowledge of AD at molecular level, give new suggestions for deeply investigating metallothionein III and brain acid soluble protein 1 in AD.

Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1124
DOIs
Publication statusPublished - Aug 15 2019

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Keywords

  • Alzheimer's Disease
  • Diet
  • Mass spectrometry, Personalized medicine
  • TgCRND8 mice
  • Top down proteomics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

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