Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal motor neuron disorder. It results in progressive degeneration and death of upper and lower motor neurons, protein aggregation, severe muscle atrophy and respiratory insufficiency. Median survival with ALS is between 2 and 5 years from the onset of symptoms. ALS manifests as either familial ALS (FALS) (~10%...

Disruption of endoplasmic reticulum (ER) proteostasis is a salient feature of amyotrophic lateral sclerosis (ALS). Upregulation of ER foldases of the protein disulfide isomerase (PDI) family has been reported in ALS mouse models and spinal cord tissue and body fluids derived from sporadic ALS cases. Although in vitro studies suggest a neuroprotective role of PDIs in ALS, the possible contributi...

Abstract Gene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS lead to severe forms amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation is also observed in other diseases, with unknown consequences. Here, we show that drives behavioral abnormalities knock-in mice, including locomotor hyperactivity and alterations social interactions, absence widespread neur...

UNLABELLED Genetic variants in UBQLN1 gene have been linked to neurodegeneration and mutations in UBQLN2 have recently been identified as a rare cause of amyotrophic lateral sclerosis (ALS). OBJECTIVE To test if genetic variants in UBQLN1 are involved in ALS. METHODS 102 and 94 unrelated patients with familial and sporadic forms of ALS were screened for UBQLN1 gene mutations. Single nucleot...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron (MN) disease. The gene encoding superoxide dismutase 1 (SOD1) is a causative element of familial ALS. Animal ALS models involving SOD1 gene mutations are widely used to study the underlying mechanisms of disease and facilitate drug discovery. Unfortunately, most drug candidates have failed in clinical trials, potentially du...

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motor neuron degeneration and neurofilament aggregate formation. Spinal motor neurons in ALS also show a selective suppression in the levels of low molecular weight neurofilament (NEFL) mRNA. We have been interested in investigating the role of microRNAs (miRNAs) in NEFL transcript stability. MiRNAs are small, 2...

Wnt5a, a member of the Wnt gene family, encodes a cysteine-rich growth factor involved in signal transduction during growth and differentiation. The Fzd2 gene codes for a cell membrane receptor called Frizzled-2 have a structure similar to G protein coupled receptors. The extracellular N-terminal of the Fzd2 receptor has a cysteine-rich domain (CRD) that binds Wnt ligands and thus primes the Wn...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons (MNs) that causes skeletal muscle paralysis. Familial forms of ALS are linked to mutations in the superoxide dismutase-1 (SOD1) gene. The mechanisms of human SOD1 (hSOD1) toxicity to MNs are unknown. We hypothesized that skeletal muscle is a primary site of pathogenesis in ALS that triggers MN degeneration...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which attacks the motor system. Current treatment for sporadic ALS or Cu, Zn superoxide dimutase 1 (SOD 1 mutation) familial ALS, produces only a modest increase in survival. Riluzole, has been available since 1995 and remains the only disease modifying therapy available for ALS. Using the statistical motor unit number est...

Escherichia coli strains carrying the Bacillus subtilis acetolactate synthase (ALS) gene were previously shown to produce less acetate with higher ATP yields. Metabolic flux analysis was used to show that excess pyruvate was channeled into the less inhibitory product, acetoin. To further understand the role of intrinsic enzymatic properties and the effect of variations in enzyme levels in the a...