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Transient inactivation of hypothalamic hormone release to prevent post-traumatic...

Transient inactivation of hypothalamic hormone release to prevent post-traumatic stress sensitization Stress is the foremost consequence of human life and became a pressing societal burden through the many sensory and societal pressures that have evolved during the past decades. Severe stress induces maladaptive changes in the bra... see more

29/02/2024

MEDIZINISCHE UNIVE...

Unknown Budget

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MEDIZINISCHE UNIVERSITAET WIEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

Financing granted El organismo HORIZON EUROPE notifico la concesión del proyecto The day 2024-02-29

ERC-2022-POC2: ERC PROOF OF CONCEPT GRANTS2 Objective:Objectives:

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Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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MEDIZINISCHE UNIVERSITAET WI...

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Project duration: 17 months Date Start: 2022-09-01
End date: 2024-02-29

Project leader

MEDIZINISCHE UNIVERSITAET WIEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

participation deadline Sin fecha límite de participación.

Project description Stress is the foremost consequence of human life and became a pressing societal burden through the many sensory and societal pressures that have evolved during the past decades. Severe stress induces maladaptive changes in the brain that clinically manifest as post-traumatic stress disorder (PTSD). Despite ~4% of the population presenting PTSD, only symptomatic therapies are available. In the ’SECRET-CELLS’ ERC award, we have identified a multimodal neurocircuit that induces brain-wide sensitization to stress through the sequential recruitment of hypothalamic, midbrain and then cortical neuronal circuits. Particularly, we identified protein targets that can simultaneously affect hormone and neurotransmitter release within this circuit and whose knock-out makes mice stress resilient. Therefore, we used unbiased proteomics to select protein interactors that participate in the related signaling cascades, determined the biochemical parameters of any such interaction and the X-ray structures of the relevant protein complexes. Moreso, a high-throughput screen was established to identify inhibitors. Here, we will apply this knowledge to use interacting proteins as templates for small-molecule inhibitor discovery and hit optimization. Subsequently, we will profile the pharmacology and cytotoxicity of the candidates in vitro. Thus, we will take critical steps towards developing a ‘circuit breaker’ that can inactivate the neuronal contingents that are causal to the development of PTSD. Thereby, we will offer a fundamentally novel framework for pharmacotherapy.

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