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The ongoing development of new XO inhibitors remains critically important due to welldocumented limitations of existing therapies, including adverse effects, the emergence of resistance, interindividual variability in therapeutic responses, and the requirement for high therapeutic doses, as seen with allopurinol

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doi: 10.1016/S0171-2985(98)80028-4 142 QiuYMarquez-CurtisLAJanowska-WieczorekA

The reason for this unexpected observation was that paralysis of an essential cellular defense mechanism like autophagy leads to faster accumulation of cellular waste, which triggers an enhanced rate of cell turnover through apoptosis and compensated enhanced regeneration [151]

To further examine the impact of protein synthesis we examined the impact of decreasing the rate of protein synthesis by using a strain that expresses the constitutively active allele of AMPK CA-AAK-2 which leads to similar phenotypes to those observed during dietary restriction (24)