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To partially compensate for this, patients are often given high systemic doses, which may increase brain exposure but also lead to significant off-target toxicity

These signs include fatigue, weakness, constipation, reduced appetite, weight loss, along with numbness and tingling sensations in the extremities

Under normal conditions, Keap1 complex-mediated ubiquitination degrades Nrf2, and when confronted with oxidative stress, Keap1 complex activity is inhibited and the Nrf2/ARE pathway is activated

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Nat Chem Biol 2011;7(10):678-84

Pharmacotherapy of obesity: targets and perspectives
