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01-07-2017 | Original Paper

Misfolded SOD1 is not a primary component of sporadic ALS

Authors: Sandrine Da Cruz, Anh Bui, Shahram Saberi, Sandra K. Lee, Jennifer Stauffer, Melissa McAlonis-Downes, Derek Schulte, Donald P. Pizzo, Philippe A. Parone, Don W. Cleveland, John Ravits

Published in: Acta Neuropathologica | Issue 1/2017

Abstract

A common feature of inherited and sporadic ALS is accumulation of abnormal proteinaceous inclusions in motor neurons and glia. SOD1 is the major protein component accumulating in patients with SOD1 mutations, as well as in mutant SOD1 mouse models. ALS-linked mutations of SOD1 have been shown to increase its propensity to misfold and/or aggregate. Antibodies specific for monomeric or misfolded SOD1 have detected misfolded SOD1 accumulating predominantly in spinal cord motor neurons of ALS patients with SOD1 mutations. We now use seven different conformationally sensitive antibodies to misfolded human SOD1 (including novel high affinity antibodies currently in pre-clinical development) coupled with immunohistochemistry, immunofluorescence and immunoprecipitation to test for the presence of misfolded SOD1 in high quality human autopsy samples. Whereas misfolded SOD1 is readily detectable in samples from patients with SOD1 mutations, it is below detection limits for all of our measures in spinal cord and cortex tissues from patients with sporadic or non-SOD1 inherited ALS. The absence of evidence for accumulated misfolded SOD1 supports a conclusion that SOD1 misfolding is not a primary component of sporadic ALS.

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Title: Misfolded SOD1 is not a primary component of sporadic ALS
Authors: Sandrine Da Cruz
Anh Bui
Shahram Saberi
Sandra K. Lee
Jennifer Stauffer
Melissa McAlonis-Downes
Derek Schulte
Donald P. Pizzo
Philippe A. Parone
Don W. Cleveland
John Ravits
Publication date: 01-07-2017
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 1/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-017-1688-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Misfolded SOD1 is not a primary component of sporadic ALS

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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