Oral Curcumin Mitigates the Clinical and Neuropathologic Phenotype of the Trembl

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Oral Curcumin Mitigates the Clinical and Neuropathologic Phenotype

of the Trembler-J Mouse: A Potential Therapy for Inherited

Neuropathy

Author(s) Mehrdad Khajavi, Kensuke Shiga, Wojciech Wiszniewski,

Feng He, Chad A. Shaw, Jiong Yan, Theodore G. Wensel, G.

Snipes, and R. Lupski

Identifiers The American Journal of Human Genetics, volume 81

(2007), page 000

DOI: 10.1086/519926

Abstract

Mutations in myelin genes cause inherited peripheral neuropathies

that range in severity from adult-onset Charcot-Marie-Tooth disease

type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital

hypomyelinating neuropathy. Many myelin gene mutants that cause

severe disease, such as those in the myelin protein zero gene (MPZ)

and the peripheral myelin protein 22 gene (PMP22), appear to make

aberrant proteins that accumulate primarily within the endoplasmic

reticulum (ER), resulting in Schwann cell death by apoptosis and,

subsequently, peripheral neuropathy.

We previously showed that curcumin supplementation could abrogate ER

retention and aggregation-induced apoptosis associated with

neuropathy-causing MPZ mutants.

We now show reduced apoptosis after curcumin treatment of cells in

tissue culture that express PMP22 mutants. Furthermore, we

demonstrate that oral administration of curcumin partially mitigates

the severe neuropathy phenotype of the Trembler-J mouse model in a

dose-dependent manner.

Administration of curcumin significantly decreases the percentage of

apoptotic Schwann cells and results in increased number and size of

myelinated axons in sciatic nerves, leading to improved motor

performance. Our findings indicate that curcumin treatment is

sufficient to relieve the toxic effect of mutant aggregation-induced

apoptosis and improves the neuropathologic phenotype in an animal

model of human neuropathy, suggesting a potential therapeutic role

in selected forms of inherited peripheral neuropathies.