Curcumin Treatment Abrogates Endoplasmic Reticulum Retention and Aggregation-Induced Apoptosis Associated with Neuropathy-Causing Myelin Protein Zero–Truncating Mutants

摘要: Mutations in MPZ, the gene encoding myelin protein zero (MPZ), major constituent of peripheral myelin, can cause adult-onset, inherited neuropathy Charcot-Marie-Tooth disease, as well more severe, childhood-onset Dejerine-Sottas and congenital hypomyelinating neuropathy. Most MPZ-truncating mutations associated with severe forms result premature termination codons within terminal or penultimate exons that are not subject to nonsense-mediated decay stably translated into mutant proteins potential dominant-negative activity. However, some truncating at 3′ end MPZ escape pathway a mild phenotype. We examined functional properties escaped decay, we found frameshift disease an intracellular accumulation proteins, primarily endoplasmic reticulum (ER), which induces apoptosis. Curcumin, chemical compound derived from curry spice tumeric, releases ER-retained mutants cytoplasm accompanied by lower number apoptotic cells. Our findings suggest curcumin treatment is sufficient relieve toxic effect aggregation-induced apoptosis may potentially have therapeutic role treating selected neuropathies.