SECRET-DOCK
Financiado
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...
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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Duración del proyecto: 17 meses
Fecha Inicio: 2022-09-01
Fecha Fin: 2024-02-29
Fecha Fin: 2024-02-29
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-02-29
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2022-POC2:
ERC PROOF OF CONCEPT GRANTS2
Cerrada
hace 2 años
Líder del proyecto
MEDIZINISCHE UNIVERSITAET WIEN
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5