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In human astrocytes, S1PR1 activation by siponimod improved Ca 2+ signaling and receptor internalization (162), while it inhibited NFB by nuclear translocation of Nrf2, a regulator of antioxidant response (64)
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Future research should also investigate strategies to minimize GLP-1RA-induced gastrointestinal adverse events, potentially through drug design innovations or combination therapies, to enhance patient tolerance and adherence
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