Oral Curcumin Mitigates the Clinical and Neuropathologic Phenotype of the Trembler-J Mouse: A Potential Therapy for Inherited Neuropathy

摘要: Mutations in myelin genes cause inherited peripheral neuropathies that range severity from adult-onset Charcot-Marie-Tooth disease type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Many gene mutants severe disease, such as those the protein zero (MPZ) 22 (PMP22), appear make aberrant proteins accumulate primarily within endoplasmic reticulum (ER), resulting Schwann cell death by apoptosis and, subsequently, We previously showed curcumin supplementation could abrogate ER retention aggregation-induced associated with neuropathy-causing MPZ mutants. now show reduced after treatment of cells tissue culture express PMP22 Furthermore, we demonstrate oral administration partially mitigates phenotype Trembler-J mouse model a dose-dependent manner. Administration significantly decreases percentage apoptotic results increased number size myelinated axons sciatic nerves, leading improved motor performance. Our findings indicate is sufficient relieve toxic effect mutant improves neuropathologic an animal human neuropathy, suggesting potential therapeutic role selected forms neuropathies.