Perrine Castets Group
Department of Cell Physiology and Metabolism - Faculty of Medicine, University of Geneva
Project at a glance
Our overall goal is to better understand the mechanisms underlying muscle homeostasis and to identify pathological changes triggering muscle decline in neuromuscular diseases and aging.
By using in vitro and in vivo models, the group works on two main aspects.
The molecular mechanisms sustaining the maintenance of the synapse between the motor neuron and the muscle fiber (i.e. the neuromuscular junction, NMJ)
- Altered muscle innervation is a hallmark of several diseases associated with muscle dysfunction, such as aging. We have previously shown that deregulation of the Akt⁄mTORC1 pathway in muscle alters NMJ maintenance, which involved defective synaptic gene expression.
We now aim to decipher the role of candidate proteins ⁄ pathways, possibly downstream of Akt⁄mTORC1, in the regionalized expression of synaptic proteins and in the muscle response to denervation.
The pathomechanisms involved in Autophagic-Vacuolar Myopathies (AVM) - We have previously demonstrated that mTORC1 is a key regulator of autophagy in muscle and that a strict balance in autophagy is required to preserve muscle homeostasis.
Although previous reports have suggested that autophagic flux is blocked in AVMs, the pathogenesis of most AVMs remains unclear.
Our long-term goal is to delineate therapeutic strategies to limit or prevent muscle dysfunction in these rare neuromuscular diseases.