Table 2.
Evidence for axonal degeneration in the pathophysiology of AD, PD and ALS.
| Disease | Evidence for axonal degeneration in NDs | References |
|---|---|---|
| Alzheimer's disease | Axonal pathology triggered by Aβ precedes cell body death | Adalbert et al., 2009 |
| Axonal leakage, swollen axons, and varicosities are associated with Aβ plaques and hyperphosphorylated tau in AD brains | Xiao et al., 2011 | |
| Autophagic vesicles are linked with axonal pathology in transgenic AD mice | Sanchez-Varo et al., 2011 | |
| Microtubule-stabilizing agent Epothilone D reduces axonal dysfunction un a mouse model of tau | Zhang et al., 2012 | |
| Aβ oligomers cause microtubule depolymerization leading to altered axonal trafficking | Sadleir et al., 2016 | |
| Parkinson's disease | Alterations in axonal transport associated with α-synuclein mutations in vitro | Saha, 2004 |
| Degeneration of axons precedes loss of cell bodies in PD patients | Orimo et al., 2005 | |
| Transgenic α-synuclein mouse model shows striatal dopaminergic axonal, but not cell body, disruption | Tofaris, 2006 | |
| α-synuclein is linked with axonal degeneration which iniciates at the distal axon and continues retrograde | Orimo et al., 2008 | |
| α-synuclein rat model shows altered axonal transport | Chung C. Y. et al., 2009 | |
| Transgenic LRRK2 mouse model shows dopaminergic axonal, but not cell body, disruption | Li et al., 2009 | |
| Axonal pathology triggered by α-synuclein propagates later to the soma is associated with neuronal dysfunction | Volpicelli-Daley et al., 2011 | |
| Early decline in axonal transport associated with α-synuclein aggregation in PD patients | Chu et al., 2012 | |
| Autophagy is involved in axonal pathology and associated with α-synuclein and LRRK2 proteins | Friedman et al., 2012 | |
| Amyotrophic lateral sclerosis | Axonal pathology starts at the distal axon and continues in a “dying back” pattern in the innervated muscle fibers | Fischer et al., 2004 |
| SARM1 gene mutations are linked with ALS development | Fogh et al., 2014 | |
| Defects in axonal transport constitute a typical feature in Drosophila models of ALS | Baldwin et al., 2016 | |
| Axonal degeneration is mediated by necroptosis and inflammation in ALS | Ito et al., 2016 | |
| Potassium channel abnormalities are linked to axon degeneration in ALS mouse model | Maglemose et al., 2017 | |
| ALS-related mutations change the subcellular expression and localization of RNAs within neuronal axon | Rotem et al., 2017 |