What is SOD1 and what is its role in ALS?

Abstract. The canonical role of superoxide dismutase 1 (SOD1) is as an antioxidant enzyme protecting the cell from reactive oxygen species toxicity. SOD1 was also the first gene in which mutations were found to be causative for the neurodegenerative disease amyotrophic lateral sclerosis (ALS), more than 20 years ago.

How does SOD1 cause ALS?

The major effect of SOD1 mutations in ALS is linked to the protein aggregation and a prion-like propagation of misfolded molecules. These mutations may also lead to a loss of function of SOD1 by affecting its structure and/or interactions pattern.

How does SOD1 cause MND?

It is widely accepted that a hallmark of SOD1-associated ALS is the deposition of SOD1 into insoluble aggregates in motor neurons, probably due to a consequence of structural destabilisation and/or oxidative damage induced by gene mutations which in turn contribute to the misfolding and aggregation of SOD1 into …

Is SOD1 loss of function involved in amyotrophic lateral sclerosis?

From analysing published data from patients with SOD1–amyotrophic lateral sclerosis, we find a marked loss of SOD1 enzyme activity arising from almost all mutations.

Where is SOD1 produced?

SOD1 functions as an antioxidant protein and is ubiquitously expressed with predominant localization in the cytoplasm but it is also localized within mitochondria,373,374 the nucleus,375 and the ER. Presently, over 150 mutations in the SOD1 gene have been identified in association with FALS.

What is TDP 43 pathology?

TDP-43 is the pathological protein in ALS and FTLD-U A significant proportion of ALS patients develop cognitive deficits, often with prominent frontal lobe features [5], and are found to have additional ub-ir NCI and neurites in the frontotemporal neocortex and hippocampus [6,7].

Where is SOD1 found?

SOD1 functions as an antioxidant protein and is ubiquitously expressed with predominant localization in the cytoplasm but it is also localized within mitochondria,373,374 the nucleus,375 and the ER.

What does sod do for the body?

Superoxide dismutases (SODs) constitute a very important antioxidant defense against oxidative stress in the body. The enzyme acts as a good therapeutic agent against reactive oxygen species-mediated diseases.

How does C9ORF72 cause ALS?

In ALS, the large size of motor neurons is thought to make these cells vulnerable to impairments in normal cell function. Disruptions in C9orf72 protein function may lead to premature motor neuron cell death, resulting in the signs and symptoms of ALS.

What Happens When SOD1 is mutated?

At least 200 mutations in the SOD1 gene have been found to cause amyotrophic lateral sclerosis (ALS), a condition characterized by progressive muscle weakness, a loss of muscle mass, and an inability to control movement.

Is SOD1 gene inherited?

All the SOD1 mutations are autosomal dominantly inherited with the exception of D90A.

Where is the SOD1 gene expressed?

Superoxide dismutase 1 (SOD1) is the ubiquitously expressed and predominant dismutase in the cytoplasm.