Medizinische Universität Graz - Research portal
Selected Publication:
Ellmeier, E.
Targeting pyruvate kinase M2 to limit T cell pathogenicity in multiple sclerosis.
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2023. pp.76.
FullText
- Authors Med Uni Graz:
- Advisor:
- Angiari Stefano
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- Abstract:
- Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) that affects approximately 2.5 million people in the world. In MS, infiltration of immune cells across the blood-brain barrier into the CNS leads to progressive neuronal death, cognitive impairment, and disability. Among these immune cells, T cells are key players in the pathogenesis of MS by controlling the development of inflammation in the CNS. Studies in the field of immunometabolism have demonstrated that inflammatory responses are regulated by immune cells through the modulation of their intracellular metabolic profile, and targeting immune cell metabolism represents a novel strategy for the treatment of inflammation and autoimmunity. Pyruvate kinase (PK) is an enzyme that catalyzes the final step of glycolysis, and immune cells preferentially express the PK isoenzymes M1 (PKM1) and M2 (PKM2). PKM2 is able to translocate into the nucleus in its monomeric/dimeric form, where it performs moonlighting functions such as protein kinase activity and regulation of gene transcription. Recent works suggested that PKM2 may be a potential therapeutic target for the treatment of T cell-mediated neuroinflammation and autoimmunity. These pre-clinical studies have demonstrated that PKM2 controls the pathogenicity of T cells in the CNS and is able to modulate neuroinflammatory responses in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.