Cholesterol secosterol aldehyde adduction and aggregation of Cu,Zn-superoxide dismutase: Potential implications in ALS

Redox Biology
Lucas S DantasSayuri Miyamoto

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by degeneration of upper and lower motor neurons. While the fundamental causes of the disease are still unclear, the accumulation of Cu,Zn-superoxide dismutase (SOD1) immunoreactive aggregates is associated with familial ALS cases. Cholesterol 5,6-secosterol aldehydes (Seco A and Seco B) are reported to contribute to neurodegenerative disease pathology by inducing protein modification and aggregation. Here we have investigated the presence of secosterol aldehydes in ALS SOD1-G93A rats and their capacity to induce SOD1 aggregation. Secosterol aldehydes were analyzed in blood plasma, spinal cord and motor cortex of ALS rats at the pre-symptomatic and symptomatic stages. Seco B was significantly increased in plasma of symptomatic ALS rats compared to pre-symptomatic animals, suggesting an association with disease progression. In vitro experiments showed that both Seco A and Seco B induce the formation of high molecular weight (HMW) SOD1 aggregates with amorphous morphology. SOD1 adduction to ω-alkynyl-secosterols analyzed by click assay showed that modified proteins are only detected in the HMW region, indicating that secosterol adduction generates s...Continue Reading

Citations

Jul 3, 2020·Data in Brief·Lucas S DantasSayuri Miyamoto
Jan 27, 2021·Free Radical Research·Sayuri MiyamotoLucas G Viviani
Mar 18, 2021·Antioxidants & Redox Signaling·Marilene DemasiLeonor Thomson
Nov 2, 2020·Archives of Biochemistry and Biophysics·Bianca S TakayasuJanice Onuki
Aug 14, 2020·Archives of Biochemistry and Biophysics·Sze M LoLia S Nakao
Feb 6, 2019·Chemical Reviews·Paolo Di MascioJean Cadet
Jun 16, 2021·American Journal of Respiratory Cell and Molecular Biology·Alexia PerrymanIlona Jaspers

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Methods Mentioned

BETA
transgenic
transmission electron microscopy
Infrared Imaging
size exclusion chromatography

Software Mentioned

PeakView
MultiQuant
PyMOL
MASCOT
flexAnalysis
Analyst TF
Odyssey software

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