Disease ⇒ Amyotrophic lateral sclerosis {40000171} Record Keys Type:Disease Parent:[ ] Definition:Amyotrophic lateral sclerosis Details Initialisation date:2019-08-25 Other Terms:ALS LinksWickipediaMerck Manual Meta Information MedDra ID:10002026 MedDra Level:pt ICD:[ ] Category:Neurology Zone:[ ] Mechanism:[ ] Notes: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease characterised by degeneration of the upper and lower motor neurons in the brain and spinal cord; this results in focal weakness, which later progresses to affect most muscles, including the diaphragm. The condition is fatal, with patients dying of respiratory failure after a mean progression time of 3-5 years.Shared Reference Notes [1.1] - Nicotinamide produced by the Akkermansia muciniphila bacteria slowed disease progression and prolonged survival in an ALS mouse model. - Nicotinamide benefits may be linked with improvements in mitochondria function. - Nicotinamide and its intermediary molecules significantly reduced in ALS. - Nicotinamide levels were decreased in the brains of ALS patients; this reduction was associated with enhanced muscle weakness. - Ruminococcus torques and Parabacteroides distasonis worsened ALS symptoms (1) [1.2] - IL-8, IL-15, MCP-1 and VEGF-A levels were significantly lower in patients than controls, while others did not show a different distribution among groups. - IP-10 levels were positively correlated with survival. [#Short Chain Fatty Acid] - The fecal SCFA concentrations (µmol/g) were not significantly different between ALS patients and controls, or between patients with different clinical characteristics. [1.3] [#Parkinson’s Disease] [#Escherichia coli] - E. coli genes promote neurodegeneration. - Two of these genes, csgA and csgB, code for proteins that form #Curli, one type of bacterial amyloid fibers. - #Curli cross-seeds and colocalizes with α-syn both in C. elegans neurons and human neuroblastoma cells. - #Curli-induced α-syn aggregations down-regulate mitochondrial genes, causing energy failure in neurons. - #Curli may have general effects in promoting neuropathologies induced by different aggregation-prone proteins, such as A-β in #Alzheimer’s disease, Huntingtin in #Huntington’s Disease, and SOD1 in amyotrophic lateral sclerosis. [1.4] [1.5] - Greater abundance of #Ruminococcus, at genus level > related to higher risk of ALS. - #kynurenine > risk factor of ALS. [1.6] - In spinal motor neurons human induced pluripotent stem cell lines > elevated levels of #Arachidonic acid. - Pharmacological reduction of #Arachidonic acid levels > reverse ALS-related phenotypes in both human sMNs and in vivo in Drosophila and SOD1G93A mouse models. [1.7] - ALS in mice> altered bacterial community related to autoimmunity (e.g., #Clostridium sp. ASF502, #Lachnospiraceae bacterium A4), inflammation (e.g., #Enterohabdus Muris,), and metabolism (e.g., #Desulfovibrio fairfieldensis) at 1- and 2-month-old SOD1G93A mice, suggesting the early microbial contribution to the pathological changes. [1.8] - The gut microbial communities of the ALS patients were more diverse and were deficient in #Prevotella spp. compared with those of their spouses. - Predictive analysis of microbial enzymes revealed that ALS patients had decreased activity in several metabolic pathways, including carbon metabolism, #Butyrate metabolism, and systems involving histidine kinase and response regulators. [1.9] - ALS > greater abundance of Escherichia coli and Enterobacteria and lower abundance of yeasts and Clostridium in the patient group [#Lactobacillus rhamnosus] - Lacticaseibacillus rhamnosus HA-114 is neuroprotective in C. elegans models of amyotrophic lateral sclerosis and #Huntington’s Disease. - neuroprotection from L. rhamnosus HA-114 is unique from other L. rhamnosus strains and resides in its fatty acid content. - dietary intervention with L. rhamnosus HA-114 restores lipid homeostasis and energy balance through mitochondrial β-oxidation. [1.11] - Tissue sections from different regions of the CNS of ALS patients contain fungi. - fungal structures such as yeast and hyphae in the motor cortex, the medulla and the spinal cord, in eleven patients with ALS. - Some fungal structures were localized intracellularly and even intranuclearly, indicating that this infection is not the result of post-mortem colonization. - PCR analysis and next generation sequencing of DNA extracted from frozen neural tissue identified a variety of fungal genera including #Candida, #Malassezia, #Fusarium, #Botrytis, #Trichoderma and #Cryptococcus. [1.12] [#Alzheimer’s disease] - extracellular #Glutamate leads to excitotoxicity in vitro and in vivo in astrocytes and neurons through the overactivation of ionotropic #Glutamate receptors. - Chronic excitotoxicity is hypothesized to play a role in numerous neurodegenerative disorders, including AD, ALS, and #Huntington’s Disease [#Alzheimer’s disease, #Multiple Sclerosis] - ALS appeared to be less associated with microbial dysbiosis compared to MS and AD, with only one microbe genus, #Methanobrevibacter and #Ruminococcaceae being commonly present under elevated conditions, respectively. - the administration of #Butyrate in the ALS mice model (G93A) alleviated the disease symptoms. [1.13] - Dysregulation of the NLRP3 inflammasome has been implicated in the progression of several neurodegenerative disorders, such as Alzheimer’s disease, #Parkinson’s Disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. [1.14] [#Alzheimer’s disease, #Multiple Sclerosis, #Parkinson’s Disease] - #Ferulic acid (FA), which occurs naturally as the feruloylated #Sugar ester in grains, fruits, and vegetables, is critical for combating #Oxidative stress and alleviating neurodegenerative diseases resulting from free radical-generated protein aggregates in brain cells. - #Ferulic acid esterases (FAE) of the gut microbiota are critical enzymes that facilitate FA release from feruloylated #Sugar ester conjugates and influence systemic health. [1.15] [#Alzheimer’s disease, #Parkinson’s Disease] - the abundance of bacteria from the #Prevotella genus negatively correlates with the pathogenicity and prevalence of different PCDs, including ALS, PD, and a mouse AD model > neuroprotective role of #Prevotella spp.References Notes[ ]
