Expansion of a hexanucleotide repeat (HRE), GGGGCC, in the C9ORF72 gene is recognized as the most common cause of familial amyotrophic lateral sclerosis (FALS), frontotemporal dementia (FTD) and ALS-FTD, as well as 5-10% of sporadic ALS.
Interestingly, SOD1 is not only responsible for fALS but may also play a significant role in sporadic ALS; therefore, SOD1 represents a promising therapeutic target.
Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial amyotrophic lateral sclerosis (ALS) patients, which were already present in presymptomatic carriers of ALS gene mutations.
Mutations in the superoxide dismutase gene (SOD1) are one cause of familial amyotrophic lateral sclerosis [ALS; also known as motor neuron disease (MND)] in humans.
Mutation of the human gene superoxide dismutase (hSOD1) triggers the fatal neurodegenerative motorneuron disorder, familial amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease).
Abnormal assemblies formed by misfolded superoxide dismutase-1 (SOD1) proteins are the likely cause of SOD1-linked familial amyotrophic lateral sclerosis (fALS) and may be involved in some cases of sporadic ALS.
To classify familial amyotrophic lateral sclerosis (FALS) on the base of family history, and to determine whether frequency of mutations in major amyotrophic lateral sclerosis (ALS) genes varies in different FALS categories.
Familial amyotrophic lateral sclerosis (fALS) accounts for 10% of ALS cases, and about 25% of fALS cases are due to mutations in superoxide dismutase 1 (SOD1).
Pathogenic mutations in the gene encoding TDP-43, TARDBP, have been reported in familial amyotrophic lateral sclerosis (FALS) and, more recently, in families with a heterogeneous clinical phenotype including both ALS and frontotemporal lobar degeneration (FTLD).
We clarified the clinical and pathological aspects of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R heterozygous mutation in the Miyakonojo Basin, a region in southern Japan where the prevalence of ALS is 11.4 per 10(5) of the population.
Misdiagnosis of fALS can be attributed to one of the following situations: (i) atypical phenotype ALS with a multidegenerative profile; (ii) unusually long lasting ALS with mild motor neuron involvement; (iii) significant clinical heterogeneity between affected family members; (iv) low reliability of family history; (v) existence of an unknown or unexpected mode of transmission; and (vi) other multidegenerative disorders with motor neuron involvement.
These studies show that, in addition to the previously demonstrated histological and electromyographic deficits, this transgenic mouse also presents changes in motor function reminiscent of the human disease, reinforcing and extending its validity as an animal model of familial amyotrophic lateral sclerosis (FALS) and allowing the investigation of novel drug treatment for ALS.
Some cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), suggesting that oxidative damage may play a role in ALS pathogenesis.
The recognition of mutations in the copper/zinc superoxide dismutase (SOD1) gene in familial amyotrophic lateral sclerosis (FALS) has been a landmark in ALS research.
Familial amyotrophic lateral sclerosis (FALS) constitutes 5 to 10% of cases of ALS and, in most families, its inheritance is consistent with an autosomal dominant trait with age-dependent penetrance.