KEGG Pathway Report
Basic Information
| ID | hsa05014 |
|---|---|
| Name | amyotrophic lateral_sclerosis_als |
| Brief Description | Amyotrophic lateral sclerosis (ALS) |
| Full Description | 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. |
hsa05014 related genes in MK4MDD (count: 19)
| Approved Symbol | Approved Name | Type | No. of Studies (Positive/Negative) |
|---|---|---|---|
| NEFH | neurofilament, heavy polypeptide | Protein mapped | 0(0/0) |
| NEFM | neurofilament, medium polypeptide | Protein mapped | 0(0/0) |
| GRIN2A | glutamate receptor, ionotropic, N-methyl D-aspartate 2A | Literature-origin; Protein mapped | 2(2/0) |
| GRIA2 | glutamate receptor, ionotropic, AMPA 2 | Literature-origin | 1(1/0) |
| BAX | BCL2-associated X protein | Literature-origin | 1(1/0) |
| SOD1 | superoxide dismutase 1, soluble | Protein mapped | 0(0/0) |
| TNFRSF1B | tumor necrosis factor receptor superfamily, member 1B | Literature-origin; Protein mapped | 2(2/0) |
| BCL2L1 | BCL2-like 1 | Literature-origin | 1(1/0) |
| GRIA1 | glutamate receptor, ionotropic, AMPA 1 | Literature-origin; Protein mapped | 1(1/0) |
| NOS1 | nitric oxide synthase 1 (neuronal) | Literature-origin | 1(0/1) |
| CYCS | cytochrome c, somatic | Protein mapped | 0(0/0) |
| TNF | tumor necrosis factor | Literature-origin; SNP mapped; Protein mapped | 5(5/0) |
| SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | Literature-origin; Protein mapped | 3(3/0) |
| TNFRSF1A | tumor necrosis factor receptor superfamily, member 1A | Literature-origin; Protein mapped | 1(1/0) |
| GRIN2B | glutamate receptor, ionotropic, N-methyl D-aspartate 2B | Literature-origin; Protein mapped | 2(2/0) |
| NEFL | neurofilament, light polypeptide | Protein mapped | 0(0/0) |
| MAPK12 | mitogen-activated protein kinase 12 | Literature-origin | 1(1/0) |
| CAT | catalase | Literature-origin | 1(1/0) |
| GRIN1 | glutamate receptor, ionotropic, N-methyl D-aspartate 1 | Protein mapped | 0(0/0) |