neurodegenerative disorders such as huntingtons disease, alzheimers disease, parkinsons disease, amyotrophic lateral sclerosis, spinal muscular atrophy, friedreichs ataxia, and others are multi-factorial illnesses in which many pathways (still poorly understood) act serially and in parallel to give a determined pathologic phenotype. thus, presently there are no effective cures for these disease...

Mutation of the ubiquitous cytosolic enzyme Cu/Zn superoxide dismutase (SOD1) is hypothesized to cause familial amyotrophic lateral sclerosis (FALS) through structural destabilization leading to misfolding and aggregation. Considering the late onset of symptoms as well as the phenotypic variability among patients with identical SOD1 mutations, it is clear that nongenetic factor(s) impact ALS et...

UNLABELLED Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. SOD-1 catalyses the superoxide radical (O(-2)) into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diag...

We report two cases of Alzheimer disease (AD)--one of them familial--in which the patient also had amyotrophic lateral sclerosis (ALS), and one patient with familial AD who had a son with ALS. Three further cases of probable ALS were found in pedigrees of AD reported from the literature. It is proposed that this association is not coincidental, but may suggest an etiological factor in common.

Human wild-type superoxide dismutase-1 (wtSOD1) is known to coaggregate with mutant SOD1 in familial amyotrophic lateral sclerosis (FALS), in double transgenic models of FALS, and in cell culture systems, but the structural determinants of this process are unclear. Here we molecularly dissect the effects of intracellular and cell-free obligately misfolded SOD1 mutant proteins on natively struct...

Mechanisms of human mutant superoxide dismutase 1 (SOD1)-induced toxicity in causing the familial form of amyotrophic lateral sclerosis (ALS) remain elusive. Identification of new proteins that can selectively interact with mutant SOD1s and investigation of their potential roles in ALS are important to discover new pathways that are involved in disease pathology. Using the yeast two-hybrid syst...

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease in which motor neurons in the brain and spinal cord degenerate by largely unknown mechanisms. ALS is familial (FALS) in 10% of cases, and the inheritance is usually dominant, with variable penetrance. Mutations in copper/zinc super oxide dismutase (SOD1) are found in 20% of familial and 3% of sporadic ALS cases. Five families wi...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that is characterized by a progressive loss of upper and/or lower motor neurons (Bruijn et al., 2004). Dysfunction and death of these neurons lead to muscle weakness, atrophy and spasticity. A fatal event for the majority of patients is a failure of the respiratory muscles, which generally occurs within one to five years of dis...

Identifying disease genes implicated in late-onset neurodegenerative disorders can be challenging due to the lack of DNA samples from multiple affected family members. To overcome this limitation, Smith et al. (2014) report in this issue of Neuron the first exome-wide rare variant analysis in unrelated familial amyotrophic lateral sclerosis (ALS) patients associating TUBA4A with ALS.

amyotrophic lateral sclerosis (als), the most common form of motor neuron disease, is a progressive and devastating disease involving both lower and upper motor neurons, typically following a relentless progression towards death. therefore, all efforts must be made by the clinician to exclude alternative and more treatable entities. als with laboratory abnormalities of uncertain significance is...