| First Author | Lucero EM | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 11 | Pages | 105288 |
| PubMed ID | 36304124 | Mgi Jnum | J:330632 |
| Mgi Id | MGI:7379917 | Doi | 10.1016/j.isci.2022.105288 |
| Citation | Lucero EM, et al. (2022) Increased KIF11/kinesin-5 expression offsets Alzheimer Abeta-mediated toxicity and cognitive dysfunction. iScience 25(11):105288 |
| abstractText | Previously, we found that amyloid-beta (Abeta) competitively inhibits the kinesin motor protein KIF11 (Kinesin-5/Eg5), leading to defects in the microtubule network and in neurotransmitter and neurotrophin receptor localization and function. These biochemical and cell biological mechanisms for Abeta-induced neuronal dysfunction may underlie learning and memory defects in Alzheimer's disease (AD). Here, we show that KIF11 overexpression rescues Abeta-mediated decreases in dendritic spine density in cultured neurons and in long-term potentiation in hippocampal slices. Furthermore, Kif11 overexpression from a transgene prevented spatial learning deficits in the 5xFAD mouse model of AD. Finally, increased KIF11 expression in neuritic plaque-positive AD patients' brains was associated with better cognitive performance and higher expression of synaptic protein mRNAs. Taken together, these mechanistic biochemical, cell biological, electrophysiological, animal model, and human data identify KIF11 as a key target of Abeta-mediated toxicity in AD, which damages synaptic structures and functions critical for learning and memory in AD. |
