Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients

Mutations in CuZn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) and are found in 6% of ALS patients. Non-native and aggregation-prone forms of mutant SOD1s are thought to trigger the disease. Two sets of novel antibodies, raised in rabbits and chicken, against peptides spaced along the human SOD1 sequence, were by enzyme-linked immunosorbent assay and an immunocapture method shown to be specific for denatured SOD1. These were used to examine SOD1 in spinal cords of ALS patients lacking mutations in the enzyme. Small granular SOD1-immunoreactive inclusions were found in spinal motoneurons of all 37 sporadic and familial ALS patients studied, but only sparsely in 3 of 28 neurodegenerative and 2 of 19 non-neurological control patients. The granular inclusions were by confocal microscopy found to partly colocalize with markers for lysosomes but not with inclusions containing TAR DNA binding protein-43, ubiquitin or markers for endoplasmic reticulum, autophagosomes or mitochondria. Granular inclusions were also found in carriers of SOD1 mutations and in spinobulbar muscular atrophy (SBMA) patients and they were the major type of inclusion detected in ALS patients homozygous for the wild type-like D90A mutation. The findings suggest that SOD1 may be involved in ALS pathogenesis in patients lacking mutations in the enzyme.

MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Medicinsk bioteknologi hsv//swe
MEDICAL AND HEALTH SCIENCES Medical Biotechnology Medical Biotechnology hsv//eng
amyotrophic-lateral-sclerosis; cu/zn superoxide-dismutase; motor-neuron degeneration; molecular pathology; gene mutation; linked SOD1; mutant SOD1; mice; disease; immunoreactivity
MEDICINE
MEDICIN
medicin
Medicine

Jonsson, P AndreasUmeå universitet,Klinisk kemi(Swepub:umu)aasjon95 (author)
Andersen, Peter MUmeå universitet,Neurologi(Swepub:umu)pean0001 (author)
Bergemalm, DanielUmeå universitet,Klinisk kemi(Swepub:umu)dalbem99 (author)
Graffmo, Karin SUmeå universitet,Patologi(Swepub:umu)kanerl79 (author)
Hultdin, MagnusUmeå universitet,Patologi(Swepub:umu)magn0001 (author)
Jacobsson, JohanUmeå universitet,Neurologi(Swepub:umu)joja0063 (author)
Rosquist, RolandUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)(Swepub:umu)roro0002 (author)
Marklund, Stefan LUmeå universitet,Klinisk kemi(Swepub:umu)stma0003 (author)
Brännström, ThomasUmeå universitet,Patologi(Swepub:umu)thbr0001 (author)
Umeå universitetPatologi (creator_code:org_t)

By the author/editor: Forsberg, Karin; Jonsson, P Andre ...; Andersen, Peter ...; Bergemalm, Danie ...; Graffmo, Karin S; Hultdin, Magnus; show more...; Jacobsson, Johan; Rosquist, Roland; Marklund, Stefan ...; Brännström, Thom ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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