Project outline
Key neuropathological processes in Multiple Sclerosis (MS) are inflammation, demyelination and subsequent axonal damage. When MS progresses, astrogliosis and failure of remyelination are two intermingled neuropathological features that become more evident resulting in neurodegeneration and long-lasting neurological deficits. Astrogliosis is considered as a major mechanical impediment to remyelination and axonal regeneration in MS. Firm interaction of the astrocytes with extracellular matrix proteins is likely to be involved in astrogliosis. Interestingly, tissue Transglutaminase (TG2), a multifunctional, Ca2+ dependent enzyme with pleiotropic effects can possibly mediate interactions between astrocytes and the extracellular matrix e.g. fibronectin, and facilitate aggregation of fibronectin. If so, this may impair oligodendrocyte migration and remyelination. Additionally, TG2 can enhance cell differentiation and may possibly play a role in oligodendrocyte differentiation thereby promoting remyelination.
This project aims at better understanding the role of TG2 in astrogliosis and remyelination which we consider is of great importance to improve the pathological and clinical outcome of MS.