Using transgenic mice expressing a common FALS-associated FUS mutation (FUS-R521C mice), we found that mutant FUS proteins formed a stable complex with WT FUS proteins and interfered with the normal interactions between FUS and histone deacetylase 1 (HDAC1).
The purpose of the study was to investigate and compare the expression of kinesins involved in anterograde (KIF5A, 5C) and retrograde (KIFC3/C2) axonal transport in SALS in humans and FALS in mice with the hSOD1G93A mutation.
The purpose of the study was to investigate and compare the expression of kinesins involved in anterograde (KIF5A, 5C) and retrograde (KIFC3/C2) axonal transport in SALS in humans and FALS in mice with the hSOD1G93A mutation.
Interestingly, FIG4 mutations were previously reported to be responsible for other neurodegenerative diseases such as autosomal recessive Charcot-Marie-Tooth disease type 4J and autosomal dominant amyotrophic lateral sclerosis/primary lateral sclerosis.
Rho guanine nucleotide exchange factor (RGNEF) is a novel NFL mRNA destabilizing factor that forms neuronal cytoplasmic inclusions in spinal motor neurons in both sporadic (SALS) and familial (FALS) ALS patients.
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.
The authors analyzed these genes, including SOD1, FUS, VAPB, ANG, TDP-43, FIG4, and CHMP2B, in a cohort of 15 index patients of Han Chinese descent with adult-onset FALS.
Familial amyotrophic lateral sclerosis (FALS)-linked SOD1 mutation accelerates neuronal cell death by activating cleavage of caspase-4 under ER stress in an in vitro model of FALS.
IL-17A serum concentrations were 5767 ± 2700 pg/ml (mean ± SEM) in sALS patients and 937 ± 927 pg/ml in fALS patients in comparison to 7 ± 2 pg/ml in control subjects without autoimmune disorders (p = 0.008 ALS patients vs. control subjects by Mann-Whitney test).
These results show that TXNRD1 may act as an important modifier gene of FALS and indicate that the additional thiol-redox system genes, thioredoxin and the peroxiredoxins, should also be investigated in FALS and other neurological disorders.
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 particular, we found that the removal of Cys-111 strongly reduces the ability of a range of different FALS-associated mutSOD1s to form aggregates and impair cell viability in cultured NSC-34 cells.
Here we found that co-chaperone CHIP (carboxyl terminus of Hsc70-interacting protein), together with molecular chaperones Hsc70/Hsp70 and Hsp90, associates with FALS-linked mutant SOD1 proteins in cultured human cells.
To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations.
To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations.
To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations.