Fonction du cerveau et dysfonctionnement du vieillissement et de la neurodégénérescence tardive


Austen Milnerwood

Université McGill


Domaine : neurosciences, santé mentale et toxicomanies

Programme Chercheurs-boursiers - Junior 2

Concours 2018-2019

Partenaire :

Parkinson Québec

Parkinson's disease (PD) is the most common neurodegenerative movement disorder affecting 1-5% of people aged 65. PD affects >100,000 Canadians, costs $2.5 billion a year and is a huge personal burden to patients and families. Current treatments fail to slow or stop PD, likely because few are developed by research into causes, rather than end-stage consequences of PD. Many families have PD caused by mutations in several proteins e.g., alpha-synuclein (aSyn), VPS35 and LRRK2. We will continue to explore the effects of these mutations in intact brains and try to reverse them, in the hope of protecting the brain from these causes of PD. We have discovered that the VPS35 protein interacts with LRRK2, and that together they regulate the function and recycling of many other brain proteins, including aSyn. This indicates multiple, and differing, PD mutations produce disease by disturbing critical brain cell functions in similar ways. We have studied mice with VPS35 and LRRK2 mutations engineered into their own proteins, and found many similarities between them. We also see similar changes in neurons produced from skin cells of PD patients. Brain function relies on a neuron's ability to store, process and transmit information.

This arises from electrochemical messages sent from one cell to the next, a process dependent on efficient protein transport and recycling. The cellular recycling machinery that aSyn, VPS35 and LRRK2 regulate is involved in this function and also brain cell survival. Small deficits in this system likely cause toxic stress over the many years that a brain cell has to work efficiently.

By studying these processes in mutant mice, we aim to develop treatments that reverse the imbalance produced by disease mutations. We hope this will improve brain health in the presence of these mutations and prevent the development of PD-like changes.