Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) are major neurodegenerative diseases for which there are no cures.
Protein misfolding is implicated in neurodegenerative diseases such as ALS, where mutations of superoxide dismutase 1 (SOD1) account for about 20% of the inherited mutations.
The transcription factor Nrf2 and its repressor protein Keap1 play key roles in the regulation of antioxidant stress responses and both Keap1-Nrf2 signalling and oxidative stress have been implicated in the pathogenesis of the ALS-FTLD spectrum of neurodegenerative disorders.
Repeat-associated non-AUG (RAN) translation produces toxic polypeptides from nucleotide repeat expansions in the absence of an AUG start codon and contributes to neurodegenerative disorders such as ALS and fragile X-associated tremor/ataxia syndrome.How RAN translation occurs is unknown.
ALS is a relentlessly progressive neurodegenerative disease and, to date, there are no neuroprotective therapies with significant impact on the disease course.
We propose that V234I-VAPB exhibits the characteristics of ALS in spite of not having the typical aggregation property of different mutations in various neurodegenerative diseases.
The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases.
Further SAFE analysis, including gene set sizes >100, showed that only neurodegenerative diseases (4 out of 34 disease pathways) including ALS were significantly upregulated.
Amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS/PDC) is a distinct neurodegenerative disorder characterized by ALS pathology with neurofibrillary tangles (NFTs) in the spinal cord and brain.
Cyanobacteria are ubiquitous throughout the world, so it is possible that all humans are exposed to low amounts of cyanobacterial BMAA, that protein-bound BMAA in human brains is a reservoir for chronic neurotoxicity, and that cyanobacterial BMAA is a major cause of progressive neurodegenerative diseases including ALS worldwide.
Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a fatal neurodegenerative disease found in the Chamorro people of Guam and other Pacific Island populations.
The broad spectrum neuroprotective capability and efficacy of some chaperone-based therapies in preclinical models makes these pathways attractive as targets for therapy in ALS, as well as other neurodegenerative diseases.
The GSSG/GSH balance is an important buffering system for reactive oxygen species and its involvement has been documented in ALS and other neurodegenerative disorders.
Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed.
Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is a neurodegenerative disease characterized by motor neuron degeneration, paralysis and death.
Thus, ALS has paralleled other neurodegenerative disorders, such as Alzheimer's and prion diseases, in which the inflammatory process is believed to participate directly in neuronal death.