Abstract Details

Title Mitochondrial Respiratory Chain Enzymatic Activities and UCP3 Expression in Muscles of Patients with Hereditary and Sporadic Amyotrophic Lateral Sclerosis

Topic Anterior Horn

Presentation(s) P07 - (-)

Poster/Presentation
Number 089

Objective

Background BACKGROUND: ALS is characterized by neurodegeneration of motor neurons with an unclear pathogenesis. Dysfunction of the mitochondrial RC has been found in muscles from ALS patients, but the results are controversial. Moreover, a dramatic increase of the mitochondrial uncoupling protein 3 (UCP3) has been reported in muscles of ALS patients by a single study.

Design/Methods DESIGN/METHODS: Activities of the RC enzymes (complex I, II, III, IV, I+III, II+III) and of citrate synthase were measured in muscles of controls (n=15), sporadic (n=11) and hereditary ALS patients (2 with a SOD1 and 3 with a c9ORF72 mutation) using optimized spectrophotometric assays. Superoxide dismutase enzymatic activities were also measured. Muscle sections were processed with a combined SDH/COX staining for blinded quantification of COX negative and ragged-blue fibers. Protein expression of UCP3, COX2, and SOD1 was measured by western blotting.

Results RESULTS: The activities of the mitochondrial RC enzymes did not differ between ALS patients and controls except in the coupled assay for complex II+III (p <0.05). The frequence of COX negative and ragged red fibers did not differ between patients and controls. Superoxide dismutase activities were specifically decreased in SOD1 mutant patients, but not in other ALS groups.Expression of the muscle mitochondrial uncoupling protein 3, was very variably expressed in both patients and controls, without any significant difference.

Conclusions CONCLUSIONS: Our data argue against a significant mitochondrial dysfunction as a unifying pathogenetic mechanisms in muscles of sporadic and hereditary ALS patients. UCP3 is not a useful biomarker for ALS. We speculate that the isolated defect of the coupled activities for complex II+III could arise from a secondary reduction in coenzyme Q pools in muscles of ALS patients, warranting further studies.

Authors/Disclosures
Marco Spinazzi, MD, PhD PRESENTER	No disclosure on file
Frauke Zipp, MD (University Medical Center Mainz)	Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Dr. Zipp has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Octapharma. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TEVA. The institution of Dr. Zipp has received research support from BMBF. The institution of Dr. Zipp has received research support from DFG. The institution of Dr. Zipp has received research support from PMSA. The institution of Dr. Zipp has received research support from Sanofi Genzyme. The institution of Dr. Zipp has received research support from UCB. The institution of Dr. Zipp has received research support from Eisai. The institution of Dr. Zipp has received research support from SK Life Science. The institution of Dr. Zipp has received research support from Abbott. The institution of Dr. Zipp has received research support from Actelion. The institution of Dr. Zipp has received research support from Bayer. The institution of Dr. Zipp has received research support from Servier. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with Novartis. Dr. Zipp has received personal compensation in the range of $0-$499 for serving as a Reviewer with Universite de Geneve. Dr. Zipp has received personal compensation in the range of $5,000-$9,999 for serving as a Reviewer with Oppenheim Förderpreis für Multiple Sklerose. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with EKFS. Dr. Zipp has a non-compensated relationship as a Associate Editor with Brain that is relevant to AAN interests or activities. Dr. Zipp has a non-compensated relationship as a Advisor with Science Translational Medicine that is relevant to AAN interests or activities.
	No disclosure on file
Leonardo Salviati, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
Elena Pegoraro, MD, PhD (University of Padova)	No disclosure on file
	No disclosure on file
Corrado Angelini, MD, FAAN (Università Di Padova)	Dr. Angelini has nothing to disclose.

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