TABLE 1.
Motor neuron disease-associated mutations and axonal pathology.
| Disease | Gene | Protein | Axonal pathology |
| ALS1 | SOD1 | Superoxide dismutase 1 | Impaired transport of mitochondria, microtubule stability, modulation of motor proteins via p38 MAP kinase etc. |
| ALS2 | ALS2 | Alsin | Impaired endocytic trafficking, signaling endosomes |
| ALS5/SPG11 | SPG11 | Spatacsin | Axonal destabilization, reduced tubulin acetylation, reduced anterograde vesicle transport |
| ALS6 | FUS | FUS | Defective transport of mitochondria, aberrant microtubule acetylation, NMJ deformity, aberrant axon branching, Fos-B overexpression |
| ALS8 | VAPB | Vesicle-associated membrane protein-associated protein B | Impaired transport of mitochondria and vesicles |
| ALS10 | TARDBP | TAR DNA-binding protein 43 | Defective transport of mitochondria and mRNP granules; reduced expression of dynactin 1; aberrant microtubule stability/acetylation |
| ALS17 | CHMP2B | Charged multivesicular body protein 2B | Impaired endocytic trafficking, signaling endosomes |
| ALS12 | OPTN | optineurin | Progressive dysmyelination and axonal degeneration through engagement of necroptotic machinery in the CNS, including RIPK1 |
| ALS18 | PFN1 | Profilin l | Decreased bound actin levels and can inhibit axon outgrowth. Primary motor neurons expressing mutant PFN1 display smaller |
| ALS22 | TUBA4A | Tubulin, alpha 4a | Destabilization of microtubules, general transport defect |
| ALS23 | ANXA11 | annexin All | Molecular tether between lysosomes and RNA granules in axon |
| ALS25/SPGIO | KIF5A | Kinesin heavy chain | Reduced kinesin-1 mediated transport, impaired neurofilament transport |
| FALS/HMN7B/Perry syndrome | DCTN1 | Dynactin 1 (p150, glued homolog, Drosophila) | Altered axonal transport and vesicle trafficking, impaired signaling endosome trafficking |
| FTDALS1 | C9orf72 | C90RF72 | Defective transport of mitochondria |
| SPG4 | SPAST | Spastin | Destabilization of microtubules, impaired transport of mitochondria and vesicles |
| SPG30 | KIF1A | Kinesin Family Member 1A | Reduced kinesin-3 mediated transport |
| SBMA | AR | Androgen receptor | Defective retrograde and anterograde transport, modulation of motor proteins via JNK |
Modified from Maday et al. (2014); De Vos and Hafezparast (2017), and Ghasemi and Brown (2018). Also refer to OMIM (https://www.omim.org/) as of June 2019.