Adenosine A2A Receptor Stimulation Shows Promise in Niemann-Pick Type C
A study investigating whether stimulation of adenosine A2A receptors (A2AR) could promote oligodendrocyte differentiation and myelin formation in patients with Niemann-Pick type C (NPC) suggested this pathway could be exploited to correct dysmyelination in these patients. Patients with NPC have mutations in the npc1 gene, resulting in intracellular accumulation of unesterified cholesterol in the endosomal/lysosomal system and subsequent cell death.
The investigators developed a pharmacological model that exposed primary cultures of oligodendrocyte progenitors (OPs) to a cholesterol transport inhibitor to induce an NPC1-like phenotype characterized by several features typical of NPC, including cholesterol accumulation, altered mitochondrial morphology and membrane potential, defect of autophagy, and maturation arrest. When an A2AR agonist known as CGS21680 was applied, it normalized all NPC1-like features.
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De Nuccio C, Bernardo A, Ferrante A, et al. Adenosine A2A receptor stimulation restores cell functions and differentiation in Niemann-Pick type C-like oligodendrocytes. Sci Rep. 2019;9(1):9782. doi: 10.1038/s41598-019-46268-8.