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Furthermore, neuroprotective and disease-modifying agents, including histone deacetylase 6 (HDAC6) inhibitors and metabolic regulators like metformin, show mechanistic promise but face challenges such as poor solubility, rapid clearance, non-specific distribution, and low brain bioavailability 17,18,19,20

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Reduced folic acid and methionine lead to a compromised supply of methyl moiety for epigenetic and metabolic regulation, in turn aggravating apoptosis and DNA damage in cultured hippocampal neurons [40,41]