Table 1.
Mutations in axonal transport deficits of neurodegenerative diseases.
| Gene | Function | Mutant | Affected axonal transport process | References |
|---|---|---|---|---|
| Alzheimer’s disease | ||||
| APP | Positively influence metabolism after non-amyloidogenic processing | Tg2576 | Anterograde axonal transport of mitochondria | Calkins et al. (2011) |
| 5 × FAD | Kinesin expression | Wang et al. (2019) | ||
| Microtubule stabilization | Choi et al. (2017) | |||
| J20 | Motor adaptor protein binding to motor | Tammineni et al. (2017) | ||
| MAPT | Helps assembly, stabilization, and modulation of microtubules | 2A, 3A, 3D | Microtubule stabilization | Shahpasand et al. (2012) |
| K369I | Cargo binding to motor proteins | Ittner et al. (2009) | ||
| Frontal temporal dementia | ||||
| MAPT | Helps assembly, stabilization, and modulation of microtubules | P301L | Anterograde axonal transport of mitochondria | Gilley et al. (2012) |
| R5L | Axonal transport of synaptophysin via activation of PP1 | Combs et al. (2021) | ||
| Amyotrophic lateral sclerosis | ||||
| SOD1 | Protect the cell from reactive oxygen species toxicity | G93A | Retrograde axonal transport of signaling endosomes via activation of p38 MAPK | Gibbs et al. (2018); Tosolini et al. (2022) |
| Anterograde axonal transport of mitochondria | Magrané et al. (2014) | |||
| Phosphorylate kinesin via activation of p38 MAPK | Morfini et al. (2013) | |||
| VAPB | Tethering molecule at the membrane contact sites between the endoplasmic reticulum and intracellular organelles | P56S | Anterograde axonal transport of mitochondria | Mórotz et al. (2012) |
| DCTN1 | Cofactor of cytoplasmic dynein that mediate most retrograde axonal transport | T1249I M571T R785W R1101K | Unknown effect but shown to affect retrograde axonal transport | Münch et al. (2004); Mäki-Marttunen et al. (2020) |
| KIF5A | Heavy chain of kinesin that mediate diverse anterograde axonal transport | KIF5AΔExon27 | Cargo binding to motor proteins | Baron et al. (2022) |
| TUBA4A | Microtubule component that maintain neuronal process and synaptic function | W407X | Microtubule stabilization | Smith et al. (2014) |
| TDP-43 | Repressor of cryptic exon inclusion during RNA splicing | G287S N390S A382T | Deacetylation modification of α-tubulin via HDAC6 | Hubbert et al. (2002); Kim et al. (2010); Fazal et al. (2021) |
| C9orf72 | A predicted guanine exchange factor | Hexanucleotide repeat expansion | Translocation of dynein and kinesin on microtubule | Fumagalli et al. (2021) |
| Parkinson’s disease | ||||
| SNCA | Synaptic transmission | A30P | Decrease kinesin expression | Chu et al. (2012) |
| E46K | Anterograde axonal transport of mitochondria | Prots et al. (2018) | ||
| E57K | Phosphorylation of tau via GSK3β and stabilization of microtubules | Prots et al. (2018); Grassi et al. (2019) | ||
| Huntington’s disease | ||||
| HTT | Synaptic neurotransmission | polyQ expansion | Retrograde transport of BDNF via HAP1 | Pardo et al. (2010) |
| Mitochondrial structural damage and anterograde axonal transport via activation of Drp1 | Shirendeb et al. (2012) | |||
APP: amyloid precursor protein; MAPT: microtubule associated protein tau; PP1: protein phosphatase 1; SOD1: superoxide dismutase 1; p38 MAPK: p38 mitogen-activated protein kinase; VAPB: vesicle-associated membrane protein B; DCTN1: dynactin subunit 1; KIF5A: kinesin family member 5A; TDP-43: TAR DNA binding protein 43; HDAC6: histone deacetylase 6; SNCA: α-synuclein; GSK3β: glycogen synthase kinase 3β; HTT: huntingtin; BDNF: brain-derived neurotrophic factor; HAP1: huntingtin-associated protein 1; Drp1: dynamin-related protein 1.