We then investigated whether the clinical course of FALS mice could be modified by the reduced expression of MTs, by crossing the FALS mice with MT-I- and MT-II-deficient mice.
In our ALS population, the observed mutational frequency of ANG gene accounts for about 1.2%, with an overrepresentation of FALS (2.3%) compared to SALS (1%) cases.
In conclusion, our findings of genetic alterations in the ARHGEF28 gene in cases of FALS suggest that a more comprehensive genetic analysis would be warranted.
Recent studies of neuroprotective agents in the FALS model show that inhibition of oxidative mechanisms (copper chelation therapy, dietary antioxidants, and coexpression of bcl-2) delays disease onset but does not extend disease duration.
Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis.
Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis.
To further assess their role in ALS, we examined these hnRNPs in spinal cord tissue from sporadic (SALS) and familial ALS (FALS) patients, including C9orf72 repeat expansion-positive patients, and controls.
Disease duration was shorter for C9ORF72 expansion carriers than for SOD1 (p<0.0001) and TARDBP (p=0.0242) carriers, other FALS (p<0.0001) and C9ORF72-negative SALS (p=0.0006).
Eight FUS mutation carriers were identified in five SALS (1%) and three FALS (7.5%), five already known and three new mutations: a de novo mutation was identified in a sporadic subject as well as the co-presence of FUS/C9ORF72 mutations in a FALS subject.
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.
An accompanying increase in depolarizing threshold electrotonus at 90 to 100 milliseconds (TEd 90-100 milliseconds) was also evident in the c9orf72FALS (P < .05) and SALS (P < .01) cohorts.
Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis.
Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis.