Molecular processes underlying neuromuscular junction denervation in humans with ALS
Aperçu du projet
Amyotrophic lateral sclerosis (ALS) is marked by dysfunction and degeneration of neuromuscular junctions (NMJ). This can be one of the earliest pathological processes observed in ALS. Past investigations demonstrated NMJ dysfunction and a period of denervation-reinnervation cycling occurs before motor neuron loss. Additionally, some evidence suggests the rescue of motor neuron loss in isolation does not improve NMJ innervation and thus has failed to slow disease progression. These findings signal the importance of NMJ-specific events to ALS pathophysiology and their potential relevance to intervention. At present, the molecular processes underlying NMJ function and denervation in ALS are poorly understood. To enhance this understanding, it is critical to study NMJs by evaluating their function, morphology, and molecular signature across the spectrum of NMJ disease states in ALS. The central hypothesis of this proposal is: molecular adaptations occur to support NMJ integrity as assessed by evaluation of the transcriptome, NMJ morphology, and NMJ function in patients with ALS.
Chef d'équipe
Matti Allen , McGill University/ The Neuro
Partenaire et Donateurs
ALS Society of Canada