Kif11 overexpression rescues cognition, long-term potentiation, and spine defects in mouse and cell models of Alzheimer's disease
Lucero, E. M.; Freund, R. K.; Johnson, N. R.; Dooling, B.; Sullivan, E.; Prikhodko, O.; Ahmed, M. M.; Dell'Acqua, M. L.; Chial, H. J.; Potter, H.
Show abstract
Competitive inhibition of kinesin motor proteins by amyloid-beta (A{beta}) may contribute to alterations in the neuronal microtubule cytoskeleton that can disrupt plasticity mechanisms required for learning and memory, such as long-term potentiation (LTP), thus contributing to synaptic dysfunction and cognitive impairments associated with Alzheimers disease (AD). Here, we tested the hypothesis that overexpression of the microtubule motor protein KIF11 (Kinesin-5/Eg5) will rescue A{beta}-mediated synaptic dysfunction and cognitive impairments. We found that overexpression of Kif11 prevented spatial learning and LTP deficits in the 5xFAD mouse model of AD and rescued A{beta}-mediated decreases in postsynaptic dendritic spine density in neuronal cultures. Together, these data suggest that KIF11 function is important for preserving synaptic structures and functions that are critical for learning and memory and for protection against A{beta}-mediated loss of cognition in AD. HighlightsO_LIDeficits in cognition and long-term potentiation in the 5xFAD mouse model of Alzheimers disease are prevented by Kif11 overexpression. C_LIO_LIA{beta}-mediated dendritic spine loss is blocked by Kif11 overexpression. C_LI
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Amelioration of symptomatic Alzheimer's Disease after selective impairment of p75NTR function in adult forebrainexcitatory neurons 98%
- Increased neuronal expression of the early endosomal adaptor APPL1 replicates Alzheimer's Disease-related endosomal and synaptic dysfunction with cholinergic neurodegeneration 96%
- Heightened β-adrenergic receptor function in the TgF344-AD rat model drives synaptic potentiation and supports learning and memory 96%
Similar papers in this journal
- Reduced firing rates of pyramidal cells in frontal cortex of APP/PS1 can be restored by acute treatment with levetiracetam 96%
- Modeling human age-associated increase in Gadd45γ expression leads to spatial recognition memory impairments in young adult mice 95%
- Age-dependent dysregulation of locus coeruleus firing in a transgenic rat model of Alzheimers disease 94%
Similar papers in this journal
- Aβ/APP-induced hyperexcitability and dysregulation of homeostatic synaptic plasticity in models of Alzheimer's disease 96%
- Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice 95%
- Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation. 95%
Similar papers in this journal
- CCR5 deficiency normalizes TIMP levels, working memory, and gamma oscillation power in APOE4 targeted replacement mice 96%
- Loss of excitatory inputs and decreased tonic and evoked activity of locus coeruleus neurons in aged P301S mice 95%
- TDP-43-M323K causes abnormal brain development and progressive cognitive and motor deficits associated with mislocalised and increased levels of TDP-43. 94%
Similar papers in this journal
- The Neurotoxin DSP-4 Dysregulates the Locus Coeruleus-Norepinephrine System and Recapitulates Molecular and Behavioral Aspects of Prodromal Neurodegenerative Disease 95%
- Axonal organelle buildup from loss of AP-4 complex function causes exacerbation of amyloid plaque pathology and gliosis in Alzheimers disease mouse model 95%
- sAPPalpha inhibits neurite outgrowth in primary mouse neurons via GABA B Receptor subunit 1a 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.