https://doi.org/10.4081/ejtm.2026.15486
38 | Effects of chronic treatment with conjugated linoleic acid on antioxidant gene expression and oxidative stress in SOD1-G93A mouse model of amyotrophic lateral sclerosis
Letizia Claudione1, B. Boccanegra1, P. Mantuano1, F. Bacchetti2, M. Milanese2, P. Bergamo3, A. De Luca1, S. Pierno1 | 1Section of Pharmacology, Dept. of Pharmacy and Drug Sciences, University of Bari Aldo Moro, Bari, Italy; 2Dept. of Pharmacy, University of Genova, Genova, Italy; 3Institute of Biosciences and Bio-Resources, CNR, Napoli, Italy.
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Published: 3 April 2026
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor-neuron disorder strongly linked to oxidative stress. The degenerative process gradually impairs motor-neurons function and leads to loss of homeostasis and integrity of skeletal muscle. Current therapies provide limited benefit, as the disease entails multiple pathological mechanisms. Among these, reduced activity of the nuclear factor erythroid 2–related factor 2 (Nrf2) has been observed, an effect that may compromise cellular antioxidant responses, inflammatory control, and mitochondrial biogenesis. In this preclinical study, we investigated the effects of conjugated linoleic acid (CLA), a natural and well-tolerated Nrf2 activator, by analysing the antioxidant enzymes gene expression in skeletal muscle of SOD1-G93A mice. CLA supplementation significantly enhanced the expression of key Nrf2 target genes, including G6PDX and NQO1 – which respectively encode for glucose-6-phosphate dehydrogenase and NADPH-quinone oxidoreductase – supporting NADPH production and redox balance. Additionally, CLA increased transcription of PPARGC1A, which encodes the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a known enhancer of Nrf2 transcription and pathway activation. These findings suggest that dietary CLA may strengthen antioxidant defences and offer support as a nutritional adjuvant in early ALS stages, potentially enhancing the overall effectiveness of current treatments.
Funded by European Union-Next Generation EU project PRIN-PNRR 2022.
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