Effect of curcumin-loaded polydopamine nanoparticles on the expression of AKT, HDAC6, and HSF1 in Trembler-J Schwann cell cultures

Charcot-Marie-Tooth is the most common progressive sensory and motor peripheral neuropathy in humans. Charcot-Marie-Tooth type 1E, a demyelinating neuropathy modeled by Trembler-J mice, affects Schwann cells due to a point mutation in the peripheral myelin protein-22 gene. Curcumin is a polyphenol extracted from the roots of Curcuma longa. Low doses of curcumin exhibit anti-inflammatory, antioxidant, antimicrobial, and neuroprotective effects, whereas high doses are used as antitumor agents because of their lethality. Delivering this compound in biological contexts has been challenging due to its predominantly hydrophobic nature. Moreover, as we have previously demonstrated, organic solvents are often used irreversibly and negatively affect Trembler-J Schwann cells. Recently, we reported the development of curcumin-loaded polydopamine nanoparticles as a promising alternative that does not require organic solvents. In this study, we assessed the in vitro neuroprotective effects of low-dose curcumin-loaded polydopamine nanoparticles in Schwann cell cultures from wild-type and Trembler-J mice. To explore curcumin’s influence on cellular detoxification pathways, we examined the expression of AKT, a key protein in the PI3K/AKT/mTOR pathway; the chaperone transcription factor HSF1; and HDAC6, a component of the autophagic process. The results show a different response between the two genotypes after five days of treatment with curcumin-loaded nanoparticles. Based on these findings, HDAC6 emerges as a candidate pathway modulated by curcumin.