| 2 | MCU knockdown in hippocampal neurons improves memory performance of an Alzheimer’s disease mouse model显示文摘Alzheimer’s disease(AD)is a progressive and degenerative disorder accompanied by cognitive decline,which could be promoted by mitochondrial dysfunction induced by mitochondrial Ca^(2+)(mCa^(2+))homeostasis Mitochondrial calcium uniporter(MCU),a key channel of mCa^(2+) uptake,may be a target for AD treatment.In the present study,we reveal for the first time that MCU knockdown in hippocampal neurons improves the memory performance of APP/PS1/tau mice through radial arm maze task.Western blot analysis,transmission electron microscopy(TEM),Golgi staining,immunohistochemistry(IHC)and ELISA results demonstrate that MCU knockdown in hippocampal neurons upregulates the levels of postsynaptic density protein 95(PSD95)and synaptophysin(SYP),and increases the numbers of synapses and dendritic spines.Meanwhile,MCU knockdown in hippocampal neurons decreases the neuroinflammatory response induced by astrogliosis and high levels of IL-1βand TNF-α,and improves the PINK1-Parkin mitophagy signaling pathway and increases the level of Beclin-1 but decreases the level of P62.In addition,MCU knockdown in hippocampal neurons recovers the average volume and number of mitochondria.These data confirm that MCU knockdown in hippocampal neurons improves the memory performance of APP/PS1/tau mice through ameliorating the synapse structure and function,relieving the inflammation response and recovering mitophagy,indicating that MCU inhibition has the potential to be developed as a novel therapy for AD. | Hongyan Cai Jing Qiao Siru Chen Junting Yang Christian Hölscher Zhaojun Wang Jinshun Qi Meina Wu | 2022 | Acta Biochimica et Biophysica Sinica2022，54，10： | 0 |
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