Figure 1.

Illustrated working model of nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) signaling in rodent peripheral neuropathy (PN). Under normal physiological conditions, Nrf2 remains bound to Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm, which ultimately leads to proteasomal degradation. (A) Under PN, Nrf2 translocates to nucleus, where it heterodimerizes with muscle aponeurosis fibromatosis (MAF) and binds to antioxidant response element (ARE). This interaction with ARE leads to the transcription of several antioxidative enzymes that can ameliorate PN conditions in rodent models by inhibiting oxidative stress, neuroinflammation, and mitochondrial dysfunction. (B) Nrf2 inducers enhance the translocation of Nrf2 or its signaling to facilitate the transcription of antioxidative enzymes, ultimately leading to alleviation of neuropathic pain conditions. This figure was created using BioRender.