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It inhibits NOTCH1 signaling by using its GCT activity to cleave a -glutamyl-cysteine bond at glutamate 1669 of the immature NOTCH receptor, thereby preventing the essential S1 cleavage and subsequent activation ( FIGURE 6 The physiological importance of this mechanism is underscored by severe developmental phenotypes upon its disruption
This lack of disease-modifying therapies highlights an urgent and unmet need for effective neuroprotective strategies capable of halting or slowing the loss of vulnerable neuronal populations
J Gastroenterol
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