In conclusion, this study demonstrates for the first time that semaglutide can maintain normal neurocytoskeletal structure, promote axonal growth and neurogenesis by downregulating the phosphorylation of HTT Ser1843 and NEFH Ser 661, and upregulating the phosphorylation of NEFL Ser473 thereby reducing the risk of developing obesity-induced cognitive impairment. Here, NEFH is linked to obesity due to melanocortin 4 receptor deficiency.