Amyotrophic Lateral Sclerosis Pathway

Preferred Label : Amyotrophic Lateral Sclerosis Pathway;

NCIt related terms : Amyotrophic Lateral Sclerosis (ALS);

Alternative definition : KEGG: Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, degenerative disorder of motor neurons. The hallmark of this disease is the selective death of motor neurons in the brain and spinal cord, leading to paralysis of voluntary muscles. Mutant superoxide dismutase 1 (SOD1), as seen in some familial amyotrophic lateral sclerosis (FALS) cases, may be toxic because it is unstable, forming aggregates in the motor neuron cytoplasm, axoplasm and mitochondria. Within mitochondria, mutant SOD1 may interfere with the anti-apoptotic function of Bcl-2, affect mitochondrial import by interfering with the translocation machinery (TOM/TIM), and generate toxic free radicals (ROS) via aberrant superoxide chemistry. These changes may then result in abnormal mitochondrial energy metabolism, Ca2 handling, and release of pro-apoptotic factors. Reactive oxygen species (ROS), produced within mitochondria, inhibit the function of EAAT2, the main glial glutamate transporter protein, responsible for most of the reuptake of synaptically released glutamate. Glutamate excess causes neurotoxicity by increasing intracellular calcium, which enhances oxidative stress and mitochondrial damage. Mutant SOD1 can also trigger oxidative reactions by various means including by increasing levels of peroxynitrite, which can then cause damage through the formation of hydroxyl radicals or via nitration of tyrosine residues on proteins. Nitration may target neurofilament proteins, disrupting their phosphorylation and affecting axonal transport. Collectively, these mechanisms (or a combination thereof) are predicted to disturb cellular homeostasis (within glial and/or motor neurons), ultimately triggering motor neuron death.;

NCIt note : This pathway originally was KEGG_ID hsa05030.;

KEGG ID : hsa05014;

Details

Origin ID

C38782;

UMLS CUI

C1521995;

Automatic exact mappings (from CISMeF team)
- Amyotrophic lateral sclerosis [ICD-11 Subcategory]
- Amyotrophic lateral sclerosis [ORDO Disease]
- Amyotrophic lateral sclerosis (disorder) [SNOMED CT concept]
- amyotrophic lateral sclerosis [MeSH Descriptor]
Semantic type(s)
- Functional Concept [UMLS semantic type]
has_gene_product_element
- 26S Proteasome Non-ATPase Regulatory Subunit 3 [NCIt concept]
- 26S Proteasome Regulatory Subunit 6A [NCIt concept]
- ATP Synthase Subunit a [NCIt concept]
- Activated Caspase-9 [NCIt concept]
- Activating Molecule In BECN1-Regulated Autophagy Protein 1 [NCIt concept]
- Annexin A11 [NCIt concept]
- Apoptosis Regulator BAX [NCIt concept]
- Apoptosis Regulator Bcl-2 [NCIt concept]
- Apoptotic Protease-Activating Factor 1 [NCIt concept]
- BH3-Interacting Domain Death Agonist [NCIt concept]
- Bcl-2-Like Protein 1 [NCIt concept]
- Bcl2 Antagonist of Cell Death [NCIt concept]
- Calcineurin Subunit B Type 1 [NCIt concept]
- Calcineurin Subunit B Type 2 [NCIt concept]
- Caspase-1 [NCIt concept]
- Caspase-3 [NCIt concept]
- Caspase-9 [NCIt concept]
- Catalase [NCIt concept]
- Cellular Tumor Antigen p53 [NCIt concept]
- Charged Multivesicular Body Protein 2b [NCIt concept]
- Cytochrome C [NCIt concept]
- Cytochrome C Oxidase Subunit 6A2, Mitochondrial [NCIt concept]
- Death Domain-Associated Protein 6 [NCIt concept]
- Derlin-1 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 3 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 6 [NCIt concept]
- Dynein Axonemal Heavy Chain 5 [NCIt concept]
- Dynein Axonemal Intermediate Chain 1 [NCIt concept]
- Excitatory Amino Acid Transporter 2 [NCIt concept]
- Glutamate Receptor 1 [NCIt concept]
- Glutamate Receptor 2 [NCIt concept]
- Glutamate Receptor Ionotropic, NMDA 2A [NCIt concept]
- Glutamate Receptor Ionotropic, NMDA 2B [NCIt concept]
- Glutamate Receptor Ionotropic, NMDA 2D [NCIt concept]
- Glutathione Peroxidase 1 [NCIt concept]
- Guanine Nucleotide Exchange Factor C9orf72 [NCIt concept]
- Heterogeneous Nuclear Ribonucleoprotein A1 [NCIt concept]
- Kinesin Heavy Chain Isoform 5A [NCIt concept]
- Kinesin-1 Heavy Chain [NCIt concept]
- Mitogen-Activated Protein Kinase 11 [NCIt concept]
- Mitogen-Activated Protein Kinase 12 [NCIt concept]
- Mitogen-Activated Protein Kinase 13 [NCIt concept]
- Mitogen-Activated Protein Kinase 14 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 5 [NCIt concept]
- Nitric Oxide Synthase, Brain [NCIt concept]
- Nuclear Pore Membrane Glycoprotein 210 [NCIt concept]
- Ras-Related C3 Botulinum Toxin Substrate 1 [NCIt concept]
- Ras-Related Protein Rab-39B [NCIt concept]
- Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Alpha Isoform [NCIt concept]
- Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Beta Isoform [NCIt concept]
- Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Gamma Isoform [NCIt concept]
- Serine/Threonine-Protein Kinase PINK1, Mitochondrial [NCIt concept]
- Serine/Threonine-Protein Kinase ULK2 [NCIt concept]
- Sigma Non-Opioid Intracellular Receptor 1 [NCIt concept]
- Spatacsin [NCIt concept]
- Superoxide Dismutase [Cu-Zn] [NCIt concept]
- Tubulin Beta-4A Chain [NCIt concept]
- Tumor Necrosis Factor [NCIt concept]
- Tumor Necrosis Factor Receptor Superfamily Member 1A [NCIt concept]
- Tumor Necrosis Factor Receptor Superfamily Member 1B [NCIt concept]
- mRNA Export Factor RAE1 [NCIt concept]
pathway_has_gene_element
- AMBRA1 wt Allele [NCIt concept]
- ANXA11 wt Allele [NCIt concept]
- APAF1 wt Allele [NCIt concept]
- BAD wt Allele [NCIt concept]
- BAX wt Allele [NCIt concept]
- BCL2 wt Allele [NCIt concept]
- BCL2L1 wt Allele [NCIt concept]
- BID wt Allele [NCIt concept]
- C9orf72 wt Allele [NCIt concept]
- CASP1 wt Allele [NCIt concept]
- CASP3 wt Allele [NCIt concept]
- CASP9 wt Allele [NCIt concept]
- CAT wt Allele [NCIt concept]
- CHMP2B wt Allele [NCIt concept]
- COX6A2 wt Allele [NCIt concept]
- CYCS wt Allele [NCIt concept]
- DAXX wt Allele [NCIt concept]
- DERL1 wt Allele [NCIt concept]
- DNAH5 wt Allele [NCIt concept]
- DNAI1 wt Allele [NCIt concept]
- GPX1 wt Allele [NCIt concept]
- GRIA1 wt Allele [NCIt concept]
- GRIA2 wt Allele [NCIt concept]
- GRIN2A wt Allele [NCIt concept]
- GRIN2B wt Allele [NCIt concept]
- GRIN2D wt Allele [NCIt concept]
- HNRNPA1 wt Allele [NCIt concept]
- KIF5A wt Allele [NCIt concept]
- KIF5B wt Allele [NCIt concept]
- MAP2K3 wt Allele [NCIt concept]
- MAP2K6 wt Allele [NCIt concept]
- MAP3K5 wt Allele [NCIt concept]
- MAPK11 wt Allele [NCIt concept]
- MAPK12 wt Allele [NCIt concept]
- MAPK13 wt Allele [NCIt concept]
- MAPK14 wt Allele [NCIt concept]
- MT-ATP6 wt Allele [NCIt concept]
- NOS1 wt Allele [NCIt concept]
- NUP210 wt Allele [NCIt concept]
- PINK1 wt Allele [NCIt concept]
- PPP3CA wt Allele [NCIt concept]
- PPP3CB wt Allele [NCIt concept]
- PPP3CC wt Allele [NCIt concept]
- PPP3R1 wt Allele [NCIt concept]
- PPP3R2 wt Allele [NCIt concept]
- PSMC3 wt Allele [NCIt concept]
- PSMD3 wt Allele [NCIt concept]
- RAB39B wt Allele [NCIt concept]
- RAB5A wt Allele [NCIt concept]
- RAC1 wt Allele [NCIt concept]
- RAE1 wt Allele [NCIt concept]
- SIGMAR1 wt Allele [NCIt concept]
- SLC1A2 wt Allele [NCIt concept]
- SOD1 wt Allele [NCIt concept]
- SPG11 wt Allele [NCIt concept]
- TNF wt Allele [NCIt concept]
- TNFRSF1A wt Allele [NCIt concept]
- TNFRSF1B wt Allele [NCIt concept]
- TP53 wt Allele [NCIt concept]
- TUBB4A wt Allele [NCIt concept]
- ULK2 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

You can consult :

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