TS4NC · Therapeutic S4N Chelation targeting Alzheimer's Disease.
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2021-03-01 → 2023-02-28
- Финансиране от ЕС
- 212 934 €
- Участници
- 1
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Кратки пептиди се изследват за способността им да регулират метални йони като медта, които допринасят за образуването на плаки в мозъка при Алцхаймер. Това помага за откриването на подходящи вещества, които да възстановят баланса на биометалите в мозъка.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
TS4NC: Therapeutic S4N Chelation targeting Alzheimer's Disease.
Despite enormous research efforts across academia and pharmaceutical industry, all clinical trials over the last decade have failed in finding a treatment for Alzheimer’s Disease (AD) which remains one of the greatest challenges in drug discovery. This neurodegenerative, progressive and irreversible brain disorder is slowly destroying the memory, cognition and ability to perform the simplest daily activities of millions of people around the world, and this number is estimated to increase to 152 million by 2050. It is suggested that healthy lifestyle with a balanced diet and both physical and mental exercise may reduce our risk of developing the condition. But the question remains, why drug development keeps failing? We believe part of the problem is that researchers focus mainly on Amyloid Cascade Hypothesis of AD, without deeper consideration of Metal Ion and Oxidative Stress Hypotheses. Herein, the TS4NC project tackled all three of them together by addressing the high level of oxidative stress produced by nonregulated redox active metal ions such as copper linked to different forms/aggregates of amyloid-β (Aβ) peptides responsible for amyloid plaque formation. This synergistic and novel strategy allowed us to conduct a comprehensive study of short peptides and shed light into discovery of the base sequence for potential drug candidate that may be involved in the redistribution and the restoration of brain biometal homeostasis.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Despite enormous research efforts across academia and pharmaceutical industry, all clinical trials over the last decade have failed in finding a treatment for Alzheimer’s Disease (AD) which remains one of the greatest challenges in drug discovery. Taking consideration all together three prevailing AD hypotheses: Amyloid Cascade, Metal Ions and Oxidative Stress, researchers conclude that loss of neurons is due to a high level of oxidative stress produced by nonregulated redox active metal ions such as copper linked to different forms/aggregates of amyloid-β (Aβ) peptides. Therefore, the regulation of metal homeostasis is a key target for drug development. Herein, we propose a new class of multifunctional agents – S4Ns, which not only sequester Cu ions from their Aβ complexes and arrest their redox cycles, thus reduce oxidative stress in the neuronal cells, inhibit Aβ aggregation, inhibit neuroglia activation and provide anti-inflammatory effects, delivering overall neuroprotection, but also put Cu back into normal physiological circulation by releasing Cu to natural Cu-carriers. The key novelty of this approach lies in that S4N mimics the N-terminus of Aβ4-x peptide (ATCUN motif), providing 4N square planar Cu(II) coordination with high affinity and selectivity. In general, S4Ns do not act as traditional chelating agents by simply eliminating metals from the organism, on the contrary they perform as Metal–Protein Attenuating Compounds (MPACs) by redistributing and assisting in the restoration of brain biometal homeostasis. This synergistic but novel strategy will allow us to carry out a comprehensive study of the new compounds and shed light into discovering promising drug candidate. Of equally importance, TS4NC MCSA will open new research horizons and significantly boost scientific career of the applicant, by helping her to reach professional maturity during the fellowship.
Оригинален текст от CORDIS (на английски).
Участници
- IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз