Interakce Notch signalizace s glykogensyntáza kinázou-3β v neurodegenerativních onemocněních

Traub, Teodor

Glycogen synthase kinase-3βeta (GSK-3β) is a serine/threonine protein kinase involved in a number of signaling processes. Pharmacological inhibition of GSK-3β has been shown to have neuroprotective effects, and its dysregulation is present in a variety of neurodegenerative, neuromuscular, developmental, and psychiatric disorders. GSK-3β is an essential component of the canonical Wnt pathway, which is involved in nervous system development. Notch signaling, like Wnt, plays a key role in development, but its relationship to GSK-3β remains unclear. The existing literature indicates that GSK-3 phosphorylates Notch intracellular domain but contradicts whether GSK3β affects Notch positively or negatively. Thus, such molecular "cross-talk" is highly complex and interactions may exist at multiple levels beyond simple phosphorylation with other components being involved. Myotonic dystrophy is a genetic neuromuscular disease that causes dysregulated protein expression of many proteins, including GSK-3β, and features developmental, muscle, and neurological symptoms. Studying molecular interactions in the context of myotonic dystrophy may help uncover effects that GSK-3β and Notch have on development and disease of nervous and muscular systems. This thesis presents a review of previous studies concerning the...

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