Project Overview

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of motor neurons and the atrophy of muscles. Approximately 4,000 Canadians are currently living with ALS, a disease diagnosed in ~1,000 citizens every year and eighty percent of people with ALS die within two to five years from diagnosis. Ten percent of ALS cases have a genetic inherited transmission, whereas the remaining ninety percent present a sporadic origin. A lot of efforts have been made in the last decades to understand the mechanisms behind this pathology, most of them focused on the events occurring to the degenerating motor neurons neglecting the extracellular environment, such as the extracellular matrix (ECM). In brain and spinal cord cells can survive, move, and communicate thanks to the support of the ECM, whose homeostasis is regulated by matrix metalloproteinases (MMPs). Surprisingly, although important, the ECM regulation, has been poorly investigated in the context of ALS. Here we hypothesize that MMPs, and an upstream molecular mediator of their release, are responsible for an excessive degradation of the ECM leading to motor neuron death in ALS.

With the development of this project, we aim at shedding light to a completely neglected mechanism in ALS, i.e. motor neuronal degeneration induced by ECM degradation, and to characterize the role of the molecular mediators responsible for this event. To achieve this, we will use a new multimodal approach combining high-end biochemical techniques and innovative fluorescence microscopy approach. Finally, the goal of this study is to unveil the potential of the newly discovered regulators as diagnostic and prognostic markers of the disease as well as new therapeutic targets to treat ALS.

Principal Investigator

Silvia Pozzi , Université Laval

Partners and Donors

ALS Canada