Format

Send to

Choose Destination
Sci Rep. 2018 Sep 21;8(1):14223. doi: 10.1038/s41598-018-31773-z.

Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis.

Author information

1
Laval University Experimental Organogenesis Research Center/LOEX, Division of Regenerative Medicine, CHU de Québec Research Center - Enfant-Jésus Hospital, Québec, Canada.
2
Department of Surgery, Faculty of Medicine, Laval University, Québec, Canada.
3
Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
4
Neuroscience Division of the CHU de Québec and Department of Medicine of the Faculty of Medicine, Laval University, Québec, QC, Canada.
5
Department of Medical Biology, Division of Anatomic Pathology and Neuropathology, CHU de Québec, Hôpital de l'Enfant-Jésus, Québec, Canada.
6
Department of Psychiatry and Neuroscience, Laval University, Québec City, Québec, Canada.
7
Centre de Recherche CERVO, Québec City, Québec, Canada.
8
Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
9
Department of Medicine (Neurology), Brain Research Center, University of British Columbia, Vancouver, BC, Canada.
10
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
11
Laval University Experimental Organogenesis Research Center/LOEX, Division of Regenerative Medicine, CHU de Québec Research Center - Enfant-Jésus Hospital, Québec, Canada. Francois.gros-louis@fmed.ulaval.ca.
12
Department of Surgery, Faculty of Medicine, Laval University, Québec, Canada. Francois.gros-louis@fmed.ulaval.ca.

Abstract

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center