University Hospital Vrije – Inflammation
Inflammation drives mitochondrial dysfunction and associated neurodegeneration in MS
Principal Investigator: Jack van Horssen, Ph.D.
Institution: University Hospital Vrije Universisteit-VUMC
Country: The Netherlands
Amount Awarded: €75,000
One of the main reasons that there are no specific therapies for progressive MS is that we know little about the processes underlying worsening disability. It has become increasingly clear that injury and loss of nervous tissue, also known as neurodegeneration, largely drives progressive MS. This team and others have shown that mitochondria, the tiny energy factories within cells, are dysfunctional in nerve cells of people with progressive MS and this may contribute to neurodegeneration. Nerve cells rely heavily on an adequate supply of energy to facilitate conduction of signals and therefore proper mitochondrial function is crucial. Eventually, impaired mitochondrial function will lead to severe nerve cell injury and loss. Now this team is unraveling which immune cells and associated inflammatory products may be responsible for mitochondrial dysfunction in nerve cells of mice and in cells isolated from people with MS.
What does this mean for people living with progressive MS?
This project will significantly contribute to our understanding of mechanisms underlying progressive MS, and provide a potential basis for the development of new therapeutics to stop neurodegeneration and progression.
The project targeted insight into inflammatory processes and mediators that contribute to mitochondrial dysfunction and subsequent neurodegeneration in progressive multiple sclerosis. The team analyzed neuronal mitochondrial alterations in grey matter regions and found reduced levels of PGC-1α, a mitochondrial master regulator, when compared to normal appearing grey matter. In vitro, treatment led to a decrease of PGC-1α, and increased the vulnerability of neurons. The team also investigated signs of mitochondrial alterations in a novel MS animal model. This model showed similar signs, resulting in correlated with neuronal loss. These data point towards a mechanism in which pro-inflammatory mediators diffuse into the cortex and lead to subsequent neuronal mitochondrial dysfunction.
Principal Investigator Jack van Horssen
Jack van Horssen, PhD, received his PhD from the Radboud University Nijmegen, The Netherlands, where he was involved in Alzheimer’s disease research. Thereafter, he moved to Amsterdam working in the field of MS neurobiology and neuropathology at the MS Center Amsterdam. His research focuses on the involvement of mitochondrial dysfunction and free radicals in MS pathology and how these processes contribute to inflammation-driven neurodegeneration. In 2010 he received the Dutch MS Fellowship and he is currently appointed as a visiting professor at the University of Hasselt in Belgium.
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