Dissertation/Thesis Abstract

Characterization of copper, zinc-superoxide dismutase aggregates: Role of disulfide bonds and pathway for aggregation
by Nakano, Yoko, M.S., California State University, Long Beach, 2009, 116; 1466293
Abstract (Summary)

ALS (Amyotrophic lateral sclerosis) is a fatal neurodegenerative disease, and it is believed that mutations in the Sod1 genes likely promote SOD1 (Cu, Zn-superoxide dismutase) aggregation and cause the disease. This study demonstrates that insoluble aggregates of SOD1 have amyloid-like characteristics and are toxic to cultured cells, although the morphology is mostly either fibrillar or non-fibrillar. Using AS SOD1 (C6A/C111S SOD1) mutants, we showed that SOD1 can form aggregates with or without disulfide bonds. However, electron microscopy revealed that intermolecular disulfide bonds are responsible for the maintenance of fibrillar aggregates and indicated that amorphous aggregates are generated much more frequently from AS SOD1 than fibrils. Moreover, we observed that AS SOD1 forms amorphous aggregates by a distinct pathway; elongated fibrillar aggregates are normally produced via spherical aggregates. The results in this study may be valuable for further investigation of the molecular mechanism of SOD1-associated ALS.

Indexing (document details)
Advisor: Cohlberg, Jeffrey
School: California State University, Long Beach
School Location: United States -- California
Source: MAI 47/06M, Masters Abstracts International
Subjects: Biochemistry
Publication Number: 1466293
ISBN: 978-1-109-17581-3
Copyright © 2020 ProQuest LLC. All rights reserved. Terms and Conditions Privacy Policy Cookie Policy