부산대학교 도서관

Primary cilium is a cellular protrusion appeared on most mammalian cell types. This organelle functions as a sensory structure receiving the extracellular milieu in response to environmental change. Neuronal ciliary membrane is highly enriched for receptors, in particular a set of certain GPCRs including melanin-concentrating hormone receptor 1 (MCHR1), determine a host of crucial physiologies. Disrupting cilia structure or function results in a spectrum of diseases collectively called ciliopathies. Common to human ciliopathies is cognitive impairment, a symptom also observed in Alzheimer's disease (AD). One hallmark of AD is accumulation of senile plaques composed of neurotoxic amyloid-β peptide, which is generated by the proteolytic cleavage of the amyloid precursor protein (APP). Here, we report that the hippocampal CA1 and the CA3 neuronal cells in AppNL-G-F knock-in mice still had canonical cilia molecule adenylyl cyclase 3- and MCHR1-positive cilia but their length were significantly changed as compared to the corresponding wild-type mice. In addition, a significant difference of cilia prevalence between NLGF- and wild-mice also observed in selective hippocampal regions. There is growing evidence that primary cilia dynamics regulate synaptic connectivity and formation of neuronal dendrites. Thus, our observations raise the important possibility that structural and functional alterations in neuronal cilia might have a role in AD development.