Project TE

Project Description

Abstract

All pathophysiological disorders from neurodegenerative diseases to diabetes, heart diseases, cancer and rare diseases are characterized by damage in structure or function of essential biological macromolecules (e.g. peptides, proteins and enzymes). The proposed research project comprises two major objectives: (i), Neurological Abeta peptide involved in Alzheimer’s disease (AD) and the effect of oxidative stress will be investigated by structural mass spectrometry (MS) in combination with bioaffinity strategies. The major interest is to obtain detailed understanding of oxidative Abeta aggregation mechanism, investigating toxic oligomeric species formed in the initial step of this process. Synthetic nitrated Abeta peptides will be used for identification, characterization and quantification of oligomers in AD mouse models. (ii), Moreover we propose to start developing new mass spectrometric based approaches for early diagnostic of treatable rare diseases. Lysosomal storage diseses (LSD’s) are a large group of rare metabolic disorders caused by the deficiency of single enzymes in metabolizing biopolymer substrates. Synthetic substrates for a few defected lysosomal enzymes will be synthesized and used for fluorimetric and mass spectrometric based diagnostic approaches. Together our data will improve the quality of methods and will increase further research interest regarding intrigue parallels existing between pathology of AD and lysosomal Niemann-Pick rare disorder.

Team members

Project Manager: Lecturer Dr. Brîndușa Alina Petre

Other Members: 

C.S.I Dr. Lucian Hrițcu

C.S.II Dr. Cristina Dimitriu

M.D. Dr. Valeriu Vasile Lupu (3 months)

Drd. Laura Ion

Drd. Claudia Andrieș

Objectives

The proposed project has the following two major objectives:

I. Characterization of oligomeric Aß species by bio-affinity mass spectrometry and the effect of their disintegration under the action of natural compounds.

II. Development of strategies to diagnose lysosomal rare diseases by fluorimetry and mass spectrometry.

 

Dissemination

Publications in which the financial support of the project is acknowledged

1. Postu, J. Noumedem, O. Cioanca, M. Hancianu, M. Mihasan, B. A. Petre*, L. Hritcu*, (2016) Lactuca capensis ameliorate beta-amyloid induced memory impairment and oxidative stress in animal model of Alzheimer’s disease, Journal of Cellular and Molecular Medicine – under review (IF 4.938)
2. Murariu, M., Ion, L., Ciobanu, C.I., Petre, B.A. and Drochioiu, G. (2016) MS, CD, and FT-IR characterization of five newly synthesized histidine-containing Ala- and Gly-based peptides. Revue Roumaine de Chimie – under review (IF 0.250)
3. Ion, L., Cozma, C., Andrieș, C., Maeser, S., Przybylski, M., Petre, B.A. Diagnosis by MRM-MS of Maroteaux-Lamy Syndrome in Dried Blood Spots Using a New Substrate. Current Topics in Medicinal Chemistry – in progress (IF 2.91)
4. Ioniță, P. A. Postu, Laura I. M. Mihașan, O. Cioanca, M. Hancianu, B. A. Petre*, L. Hritcu* Hypericumperforatum aqueous extract enhance memory formation via decreasing oxidative damage in the rat hippocampus, Biomedicine&Pharmacotherapy – in progress ( IF 2.326)
5. Andrieş, Ş. Slămnoiu, L. Ion, A. Neamţu and B. A. Petre, (2016), Cross Reactivity of Anti Nitro-Tyrosine Antibodies to Oxidative Modified Tyrosine Containing Peptides by Using a SAW-Biosensor Assay, PlosOne – in progress

Supplemental results

In addition, the infrastructure acquired by the current project was used to complete the experimental part of one PhD thesis and one Bachelor thesis. Both students were in part coordinated by Dr. Brindusa Petre, the director of the project.

PhD thesis:  Sabina Bancila, “Contribuţii la studiul extracţiei şi aplicaţiilor biomedicale şi analitice ale zeinelor din porumbul autohton” – examination date 20.12.2016

Bachelor thesis: Cornelia Irimia, ” Proteomica: metode modern de identificare şi caracterizare a proteinelor” – examination date February – 2017

Participation at scientific events where the financial support of the project was acknowledged.

• Affinity – Mass spectrometry – New Methods and Application to Protein Therapeutics Rüsselsheim am Main, Rüsselsheim am Main, Germany, November 14^th – 15^th, 2016.

1. Alina Petre – “The effect of O. Mjorana Essential Oil on an Amyloid-β (1-42) Rat Model of Alzheimer’s Disease: Cognitive and Molecular Approaches” “Affinity – Mass spectrometry – New Methods and Application to Protein Oral communication
2. Claudia Andries – “Oxidative Modification in Proteins: Cross Reactivity and Anti-Nitrtyrosine Antibodies to oxidative Modified Tyrosine containing Peptides” Oral communication

• 3^rd International Conference on Analytical Chemistry, Iasi, Romania. 28-31 August, 2016.

1. Laura Ion, Lucian Hritcu, Cristina Dimitriu, Stefan Maeser, Michael Przybylski, Brîndușa-Alina Petre – “Lysosomal Storage Diseases: MRM-MS and Fluorimetric Diagnostics” Oral communication

 

• “Alexandru Ioan Cuza” University Days, Faculty of Chemistry Conference, Iasi, Romania 27 – 28 October, 2016.

1. A. Postu, L. Ion, S. Mikkat, M. O. Glocker, B. A. Petre, L. Hritcu – “The effects of Origanummajorana L. essential oil on an amyloid beta (1-42) rat model of Alzheimer’s disease: cognitive and molecular approaches” Oral communication
2. Bancila, L. Ion, R. Stefanescu, C. Andries, B. A. Petre, G. Drochioiu – “Proteomic approach to characterize prolamins from corn”. Oral communication