ヒト脳のエネルギー代謝を支えるプリンサルベージ経路の強化

抄録

Recent studies have highlighted that xanthine oxidoreductase (XOR) inhibitors, widely used as therapeutic agents for gout, have effects beyond urate-lowering, notably impacting cellular energy metabolism. Beneficial effects on the brain and cardiovascular system have been reported following administration of allopurinol or febuxostat. Conversely, clinical observations suggest that discontinuation of XOR inhibitors may be associated with an increased risk of cardiovascular events. These findings indicate that XOR inhibition not only suppresses uric acid production but also markedly influences purine metabolism, particularly the salvage pathway-mediated ATP production mechanism. This review outlines the relevance of impaired energy metabolism in the pathophysiology of neurodegenerative diseases, and significance of the purine salvage pathway in the human brain. Furthermore, we discuss combination strategies, focusing on XOR inhibitors, which aim to enhance intracellular ATP levels.