Furthermore, human genetic evidence has linked the dysregulation of RIPK1 to the pathogenesis of ALS as well as other inflammatory and neurodegenerative diseases.
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.
Although novel ALS genetic variants have been identified, the shared genetic risk between ALS and other neurodegenerative disorders remains poorly understood.
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.
Amyotrophic lateral sclerosis (ALS: Lou Gehrig's Disease) is a lethal neurodegenerative disease of upper and lower motorneurons in the brain and spinal cord.
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.
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.
ALS is a relentlessly progressive neurodegenerative disease and, to date, there are no neuroprotective therapies with significant impact on the disease course.
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.
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.
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).
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 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.