A Cystine-Rich Whey Supplement (Immunocal®) Delays Disease Onset and Prevents Spinal Cord Glutathione Depletion in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

Antioxidants

Erika K. Ross¹  Aimee N. Winter¹  Heather M. Wilkins¹  Whitney A. Sumner¹  Nathan Duval¹  David Patterson¹  Daniel A. Linseman¹ 

[1] Department of Biological Sciences and Eleanor Roosevelt Institute, University of Denver, 2199 S. University Blvd., Denver, CO 80208, USA; E-Mails:

关键词: Immunocal^®;    whey protein;    oxidative stress;    glutathione;    cysteine;    amyotrophic lateral sclerosis;   

DOI  :  10.3390/antiox3040843

来源: mdpi

【 摘 要 】

Depletion of the endogenous antioxidant, glutathione (GSH), underlies progression of the devastating neurodegenerative disease, amyotrophic lateral sclerosis (ALS). Thus, strategies aimed at elevating GSH may yield new therapeutics for ALS. Here, we investigated the effects of a unique non-denatured whey protein supplement, Immunocal^®, in the transgenic Gly position 93 to Ala (G93A) mutant hSOD1 (hSOD1^G93A) mouse model of ALS. Immunocal^® is rich in the GSH precursor, cystine, and is therefore capable of bolstering GSH content. Transgenic hSOD1^G93A mice receiving Immunocal^® displayed a significant delay in disease onset compared to untreated hSOD1^G93A controls. Additionally, Immunocal^® treatment significantly decreased the rate of decline in grip strength and prevented disease-associated reductions in whole blood and spinal cord tissue GSH levels in end-stage hSOD1^G93A mice. However, Immunocal^® did not extend survival, likely due to its inability to preserve the mitochondrial GSH pool in spinal cord. Combination treatment with Immunocal^® and the anti-glutamatergic compound, riluzole, delayed disease onset and extended survival in hSOD1^G93A mice. These findings demonstrate that sustaining tissue GSH with Immunocal^® only modestly delays disease onset and slows the loss of skeletal muscle strength in hSOD1^G93A mice. Moreover, the inability of Immunocal^® to rescue mitochondrial GSH in spinal cord provides a possible mechanism for its lack of effect on survival and is a limiting factor in the potential utility of this supplement as a therapeutic for ALS.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.