FP7Реинтеграция2011–2015

EGCG+INSULIN= · Towards construction of a comprehensive map of amyloid-ligand interactions: (-)-Epigallocatechin 3-Gallate and insulin amyloid

7РП — „Хора“ (Действия „Мария Кюри“)

Период
2011-08-01 → 2015-07-31
Финансиране от ЕС
100 000 €
Участници
1
Схема
MC-CIG

Линиите свързват координатора с партньорите.

Накратко на български

Взаимодействията между протеините на инсулина и веществото епигалокатехин галат (EGCG) помагат за разбирането на образуването на амилоидни влакна. Тези процеси са важни за откриването на молекули, които могат да спрат натрупването на вредни протеинови структури в организма.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Towards construction of a comprehensive map of amyloid-ligand interactions: (-)-Epigallocatechin 3-Gallate and insulin amyloid

The main goal of this project was to attract and retain a young scientist working in USA to return and establish a research facility in Lithuania. As a result of the project, the Group of Amyloid Research was established at the Department of Biothermodynamics and Drug Design at the Institute of Biotechnology, Vilnius, Lithuania. The scientist, Vytautas Smirnovas, has returned to Lithuania, bringing extensive experience obtained during the work at Case Western Reserve University, USA, Technical University of Dortmund, Germany, and Institute of High Pressure Physics of Polish Academy of Sciences. The Marie Curie grant enabled the researcher to start a new research theme – biophysical studies of amyloid-like fibril formation and testing of potential antiamyloidogenic compounds. The institute did not carry out research in this field prior to the scientist's return. Together with the help of EU structural funds, European Social Fund, and Research Council of Lithuania new equipment and research reagents were purchased. One permanent staff position was established and supported by Lithuanian state budget; two additional staff positions (one of postdoc level and one of technician level) and two PhD students are supported by grants, obtained by Dr. V.Smirnovas. Eighteen undergraduate and six master’s students were/are volunteering in the group and were/are trained by the scientist. The initial idea of the project was studying inhibition of insulin amyloid-like fibril formation by epigallocatechin gallate (EGCG). Surprisingly, it was found that, contrary to previously published data, EGCG does not inhibit insulin amyloid fibril formation. It led to the expansion of the project towards other amyloidogenic proteins and potential small molecule inhibitors. Within the scope of this project and the other projects, obtained by Dr. V.Smirnovas, 265 compounds were tested as possible inhibitors of insulin, amyloid beta (Abeta), alpha-synuclein, and mouse prion protein (MoPrP) amyloid-like fibril formation. Five were identified as outstanding inhibitors of insulin fibril formation; four of them inhibited fibrillation of alpha-synuclein, one slowed down aggregation of MoPrP, but none were effective against Abeta.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Increasing number of peptides and proteins are found to form ordered fibrillar aggregates under certain conditions. Amyloid-like fibrils are associated with a number of diseases, ranging from neurodegenerative diseases to systemic amyloidoses. Current studies have shown the ability of (-)-Epigallocatechin 3-Gallate (EGCG) to inhibit fibril formation and even to dissociate fibrils. Nevertheless, some EGCG-resistant structures were also reported. To evaluate EGCG as a possible drug candidate against amyloid diseases, extensive studies of protein aggregation in presence of the ligand is necessary.The proposed research will construct a comprehensive map of EGCG-insulin amyloid interactions.1.At varying conditions insulin forms fibrils via different pathways. The impact of EGCG on the pathway of aggregation will be studied.2.At varying conditions insulin aggregates into distinct amyloid structures, mimicking prion-like ‘strains’. The impact of EGCG on insulin ‘strains’ will be studied.3.Insulin fibrils can elongate at conditions not favorable for de novo fibril formation. The impact of EGCG on fibril elongation (mimicking prion-like infectivity) will be studied.Isothermal titration calorimetry (ITC) will be used to study insulin-EGCG binding. Also ITC will be used to determine thermodynamic parameters of fibril elongation. Differential scanning and pressure perturbation calorimetry (DSC and PPC), ultrasound velocimetry, densitometry and fluorescence spectroscopy will give insight into kinetics and thermodynamics of insulin aggregation in presence of EGCG at different conditions. Fourier-transform infrared (FTIR) spectroscopy will be used to monitor changes in secondary structure, and atomic force microscopy (AFM) will show the morphology of aggregates.

Оригинален текст от CORDIS (на английски).

Участници

  • VILNIAUS UNIVERSITETAS · VilniusКоординаторЛитва

Връзки

Данни: CORDIS, © Европейски съюз