β-N-methylamino-L-alanine (L-BMAA) has been shown to induce ER stress in a variety of models and has been linked to several types of neurodegenerative disease including Guamanian amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC).
While the Alzheimer's field has begun to shift attention toward much earlier-stage (even prodromal) patients in trials intended to modify disease progression, other neurodegenerative diseases (e.g., Parkinson's, ALS and possibly HD) must now consider similar changes in approach.
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.
Together, the findings from our study may assist future development of G-quadruplex-specific ligands in the treatment of neurodegenerative diseases like ALS and FTD.
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.
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.
The neurotoxin β-<i>N</i>-methylamino-l-alanine (BMAA), a non-protein amino acid produced by terrestrial and aquatic cyanobacteria and by micro-algae, has been suggested to play a role as an environmental factor in the neurodegenerative disease Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia complex (ALS-PDC).
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.
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.
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.
Since the middle of this century, a remarkable concentration of cases of neurodegenerative disease(s), referred to as amyotrophic lateral sclerosis and Parkinson-dementia complex (ALS/PDC), has been recognized among Chamorro natives of Guam.
Similarly, the contrasting actions of NO on motor neurons may have important consequences for the potential use of nitric oxide synthase inhibitors in the treatment of ALS and other related neurodegenerative diseases.
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.
Repeat-associated non-AUG (RAN) translation is a noncanonical translation initiation event that occurs at nucleotide-repeat expansion mutations that are associated with several neurodegenerative diseases, including fragile X-associated tremor ataxia syndrome (FXTAS), ALS, and frontotemporal dementia (FTD).
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.
Postmortem human brain tissue was obtained from different brain regions of patients with ALS, normal controls (NC), and patients with AD and Lewy body dementia (LB)-neurodegenerative diseases in which motor neurons are unaffected.