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Several promising compounds have failed in clinical trials due to a range of challenges, including inadequate disease models, late intervention timing, insufficient biomarker validation, and difficulty in distinguishing symptomatic from neuroprotective effects

Large-scale human studies evaluating long-term exposure, systemic absorption, and potential adverse effects remain limited

Moreover, it has been shown that the increase in the positive charge in the N-domain and high hydrophobicity in the H-domains are potent for efficient secretion system

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