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Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis
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Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis
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Journal Article
Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis
2018
Overview
Aggregation of mutant superoxide dismutase 1 (SOD1) is a pathological hallmark of a subset of familial ALS patients. However, the possible role of misfolded wild type SOD1 in human ALS is highly debated. To ascertain whether or not misfolded SOD1 is a common pathological feature in non-
SOD1
ALS, we performed a blinded histological and biochemical analysis of
post mortem
brain and spinal cord tissues from 19 sporadic ALS, compared with a
SOD1
A4V patient as well as Alzheimer’s disease (AD) and non-neurological controls. Multiple conformation- or misfolded-specific antibodies for human SOD1 were compared. These were generated independently by different research groups and were compared using standardized conditions. Five different misSOD1 staining patterns were found consistently in tissue sections from SALS cases and the SOD1 A4V patient, but were essentially absent in AD and non-neurological controls. We have established clear experimental protocols and provide specific guidelines for working, with conformational/misfolded SOD1-specific antibodies. Adherence to these guidelines will aid in the comparison of the results of future studies and better interpretation of staining patterns. This blinded, standardized and unbiased approach provides further support for a possible pathological role of misSOD1 in SALS.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
