A step forward towards the development of treatments aimed at restoring mitochondrial function in inflammatory CNS diseases
A step forward towards the development of treatments aimed at restoring mitochondrial function in inflammatory CNS diseases Funded by the Italian Multiple Sclerosis Association, the Wellcome Trust, the European Research Council, the Evelyn Trust, the Addenbrooke's Charitable Trust, and the Bascule Charitable Trust, Stefano Pluchino, Luca Peruzzotti-Jametti and their team (Clinical Neurosciences) have been working on how to reduce the persistent brain inflammation contributing to pathogenesis of central nervous system (CNS) diseases, including multiple sclerosis. This inflammation is caused by dysfunctional mitochondria in macrophages entering the brain from the bloodstream and in brain-resident immune cells called microglia.
Recent work from the Cambridge team published in PLOS Biology has shown that functional mitochondria can be transferred to and fused with the mitochondrial network of the macrophages using extracellular vesicles secreted by neural stem cells. This process leads to metabolic reprogramming of the macrophages, and ultimately to a significant reduction of the inflammation. The researchers have observed how neural stem cells transplanted in mice manipulated to develop multiple sclerosis ameliorate clinical deficits, thanks to their extracellular vesicles actively transferring functional mitochondria to macrophages and microglia presenting a mitochondrial dysfunction.
This study clarifies how mitochondrial transfer from neural stem cells contributes to their previously observed healing ability, and is a welcome step forward in regenerative neuroimmunology.