SynLip
Financiado
MCH/COX2-depend regulation of neuronal function and neuroinflammation in Alzheim...
MCH/COX2-depend regulation of neuronal function and neuroinflammation in Alzheimer’s disease
Alzheimer’s disease (AD) patients stay in a prodromal phase over many years before robust cognitive decline. During this phase, complex molecular events lead to cellular alterations, resulting in aberrant synaptic activity and chr...
Alzheimer’s disease (AD) patients stay in a prodromal phase over many years before robust cognitive decline. During this phase, complex molecular events lead to cellular alterations, resulting in aberrant synaptic activity and chronic inflammation which leads to neuronal death and cognitive impairment. My unpublished work, shows that melanin-concentrating hormone (MCH) regulates synaptic function and revealed that the MCH system is impaired in a mouse model of early AD and AD patients. I showed that MCH regulates the neuronal expression of multiple immediate early genes that control neuronal activity, and more interestingly the expression of Ptgs2/COX2. COX2 catalyzes the formation of pro-inflammatory prostaglandins from arachidonic acid but upon activity change it produces specialized pro-resolving mediators. Thus, precise COX2 levels and activity are essential to regulate the synthesis of bioactive lipids involved in the initiation and arrest of inflammation. Ptgs2/COX2 is expressed in excitatory neurons and a link to synaptic function, seizure and neuroinflammation-associated to seizure has been established. My preliminary data shows that excitatory neurons from a mouse model of early AD that displays MCH-system dysfunction, aberrant synaptic activity and neuroinflammation have altered Ptgs2 expression. Together with genetic studies that place lipid metabolism as a mediator of microglia-mediated neuroinflammation, this suggest that COX2 can play a critical role in the neuron-microglia interaction during the prodromal phase of AD. I hypothesize that impaired MCH system leads to aberrant neuronal activity and increased Ptgs2 expression, increasing pro-inflammatory mediators and recruiting microglia activation. Here, I will study how MCH-system/Ptgs2 interaction affects neuronal lipid metabolism and test if it regulates neuron-microglia communication contributing to neuroinflammation and to the onset of cognitive decline.
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Duración del proyecto: 29 meses
Fecha Inicio: 2022-09-19
Fecha Fin: 2025-02-28
Fecha Fin: 2025-02-28
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-09-19
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
Presupuesto
El presupuesto total del proyecto asciende a
157K€
Líder del proyecto
UNIVERSIDADE DO MINHO
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5