All you can EAAT3: restoring myelin, the brain's favourite fat.

Abstract

Multiple sclerosis (MS) is one of the most common neurodegenerative disorders affecting young individuals. The high prevalence of the disease, as well as the relatively early onset (between 20 and 40 years of age) compared to other neurodegenerative disease, leads to a costly social and economic burden1,2. MS is a heterogeneous disease and can be subdivided into several forms characterised by different hallmarks. Relapse remitting MS (RRMS) is most diagnosed and is characterised by periods of relapses, where symptom severity increases, and remission, where (partial) recovery can be observed. Half of patients suffering from RRMS transition into the progressive form of the disease, secondary progressive MS (SPMS), within 20 years and currently no therapeutic approach can lower the risk of conversion3. Unfortunately, when this progressive stage of the disease is entered, the symptoms of patients only worsen, as recovery no longer occurs, and treatment options become highly limited. The third, and least common (15%) form of MS is primary progressive MS (PPMS). These patients immediately enter the progressive stage and therefore do not experience any recovery of symptoms during the course of their disease4,5. A variety of symptoms are experienced by patients with MS. These include physical impairments such as muscle weakness, spasticity, and fatigue, but also less visible symptoms such as cognitive impairment6. The most affected cognitive processes include memory, information processing, and executive functions7. The diversity of the symptoms puts an immense burden on the diagnosis and further care that patients with MS need by caregivers and healthcare providers, adding to the economic burden of the disease8. Biologically, MS can be categorised as an autoimmune disease where a patient’s immune system turns against its own body. A lot remains unknown when it comes to the cause of MS, however, it is clear that immune cell infiltration accompanied by the release of cytokines plays an important role in uncontrolled inflammation in both grey and white matter. T helper cells (CD4+ T cells) react to antigen-presenting cells and become responsive to myelin-producing oligodendrocytes. This triggers a key feature of multiple sclerosis (MS): the death of oligodendrocytes, resulting in demyelination.