Molecular Mechanisms of Synaptopathies
Mécanismes moléculaires des synaptopathies
Neurodegenerative diseases are a major issue for Public Health in Europe and their prevalence will significantly increase worldwide. There is no treatment to cure of effectively reduce the progression for the most common neurodegenerative diseases like Alzheimer (AD) or Parkinson’s (PD). Hence, it is essential to understand the early events acting at the initial state of these diseases, before irreversible neuronal damage occurs.
The key question we want to answer is how previously healthy neurons start to die. Interestingly, the decrease in synaptic density is much more accused than the loss of neurons in patients suffering neurodegenerative diseases. For instance, synaptic degeneration is a hallmark in the initial phases of AD and PD.
Therefore, deciphering how synaptic decay precedes neuronal loss is essential to fully understand the earliest steps in neurodegeneration and, by extension, the early onset in neurodegenerative diseases. Identification of central molecular players and pathways acting at the “roots of neurodegeneration” will undoubtedly open new avenues to diagnose and even treat neurodegenerative diseases before the pathological/clinical symptoms start.
To fulfill these aims, we take advantage of the powerful genetic tools available in the “fruit-fly” Drosophila -a successful model to study neurodegeneration and many other human diseases- together with ex vivo models like mouse primary cultures and human induced pluripotent stem cells (iPSC).