The response to oxidative stress involves numerous genes and mutations in these genes often manifest in pleiotropic ways that presumably reflect perturbations in ROS-mediated physiology. The Drosophila melanogaster SOD1-null allele (cSODn108) is proposed to result in oxidative stress by preventing superoxide breakdown. In SOD1-null flies, oxidative stress management is thought to be reliant on ...

Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by loss of motor neurons. With conformation-specific antibodies, we now demonstrate that misfolded mutant SOD1 binds directly to the voltage-dependent anion channel (VDAC1), an integral membrane protein imbedded in the outer mitochondrial membrane. This interaction is fo...

Oxidative stress is significant in numerous types of disease including cancer. To protect cells and organs against reactive oxygen species (ROS), the body has evolved an antioxidant protection system that involved in the detoxification of ROS. Single nucleotide polymorphisms (SNP) of anti-oxidative enzymes may dramatically change the activity of the encoded proteins; therefore, certain alleles ...

Amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease) is a neurodegenerative disease that causes the death of motor neurons controlling voluntary muscle movement. After the appearance of early symptoms such as muscle weakness/stiffness, patients with ALS suffer from progressive muscular paralysis and usually die from respiratory failure within 2 to 5 years. Riluzole and Edarav...

background: despite the genetic heterogeneity reported in familial als (fals), sod1 gene mutations are the most frequent cause of fals, accounting for around 20% of familial cases (als1) and isolated sporadic cases. mutant forms of sod1 exhibit toxicity that promotes the death of motor neurons. it is well documented that fals produces protein aggregates in the motor neurons of fals patients, wh...

Aging is characterized by increased oxidative stress, chronic inflammation, and organ dysfunction, which occur in a progressive and irreversible manner. Superoxide dismutase (SOD) serves as a major antioxidant and neutralizes superoxide radicals throughout the body. In vivo studies have demonstrated that copper/zinc superoxide dismutase-deficient (Sod1(-/-)) mice show various aging-like patholo...

An integrated approach which combines in-cell NMR spectroscopy with optical and X-ray fluorescence microscopy was developed to describe the intracellular maturation state of human Cu,Zn-SOD1. Microscopy data show a correlation between the intracellular levels of SOD1 and the content of zinc, corresponding to zinc binding to SOD1 observed by in-cell NMR.

The manner in which an animal's environment is furnished may have significant implications for animal welfare as well as research outcomes. We evaluated four different housing conditions to determine the effects of what has been considered standard rodent enrichment and the exercise opportunities those environments allow on disease progression in the amyotrophic lateral sclerosis mouse model. F...

Iron regulatory protein 1 (IRP1) is a cytosolic bifunctional [4Fe-4S] protein which exhibits aconitase activity or binds iron responsive elements (IREs) in untranslated regions of specific mRNA encoding proteins involved in cellular iron metabolism. Superoxide radical (O2.-) converts IRP1 from a [4Fe-4S] aconitase to a [3Fe-4S] "null" form possessing neither aconitase nor trans-regulatory activ...

Mice lacking Cu,Zn superoxide dismutase (SOD1) show accelerated, age-related loss of muscle mass. Lack of SOD1 may lead to increased superoxide, reduced nitric oxide (NO), and increased peroxynitrite, each of which could initiate muscle fiber loss. Single muscle fibers from flexor digitorum brevis of wild-type (WT) and Sod1(-/-) mice were loaded with NO-sensitive (4-amino-5-methylamino-2',7'-di...