| First Author | Wang Q | Year | 2019 |
| Journal | Neurobiol Dis | Volume | 127 |
| Pages | 410-418 | PubMed ID | 30923004 |
| Mgi Jnum | J:279566 | Mgi Id | MGI:6355570 |
| Doi | 10.1016/j.nbd.2019.03.021 | Citation | Wang Q, et al. (2019) Amyloid beta-mediated KIF5A deficiency disrupts anterograde axonal mitochondrial movement. Neurobiol Dis 127:410-418 |
| abstractText | Mitochondria are crucial organelles for neurophysiology and brain mitochondrial defects constitute a characteristic of Alzheimer's disease (AD). Impaired axonal mitochondrial traffic, especially the anterograde axonal mitochondrial transport is a pronouncing mitochondrial defect that underlies synaptic failure in AD-related conditions. However, the detailed molecular mechanisms of such axonal mitochondrial abnormality have not been fully understood. KIF5A is a key isoform of kinesin-1, which is a key molecular machinery in facilitating anterograde axonal mitochondrial transport. In this study, we have determined a downregulation of KIF5A in postmortem AD temporal lobes. Further experiments on amyloid beta (Abeta)-treated primary neuron culture and 5xFAD mice suggest a close association of Abeta toxicity and KIF5A loss. Downregulation of KIF5A mimics Abeta-induced axonal mitochondrial transport deficits, indicating a potential role of KIF5A deficiency in AD-relevant axonal mitochondrial traffic abnormalities. Importantly, the restoration of KIF5A corrects Abeta-induced impairments in axonal mitochondrial transport, especially the anterograde traffic, with little or no impact on retrograde axonal mitochondrial motility. Our findings suggest a novel KIF5A-associated mechanism conferring Abeta toxicity to axonal mitochondrial deficits. Furthermore, the results implicate a potential therapeutic avenue by protecting KIF5A function for the treatment of AD. |
