PRJNA719985
Proteomics and functional study reveal kallikrein-6 enhances communicating hydrocephalus by injuring the synapse of neuron
Communicating hydrocephalus (CH) is a common neurological disorder caused by block of cerebrospinal fluid and we aim to explore potential molecular mechanism. Quantitative proteomic analysis was performed to screen the differentially expressed proteins (DEPs) between patients with CH and without CH (non-CH). A rat model of CH was verified by Hoechest staining, and the co-localization of target protein and neuron was detected by immunofluorescence. The effect of KLK6 on synapse structure was assessed by functional loss experiments. A total of 11 DEPs were identified, and kallikrein6 (KLK6) was significantly up-regulated in CH patients compared to non-CH. The rat model of CH was successfully constructed and the KLK6 was co-located with NeuN in brain tissue and the expression of KLK6 in CH group was higher than that in the control group. After interfering KLK6 expression, the expression of synapsin-1 and PSD95 in neuronal cells was increased, and the length, number and structure of synapses were significantly improved. Moreover, the transcriptome profile after interference with KLK6 expression was obtained and identified 5681 differentially expressed genes (DEGs). The upregulated DEGs of Appl2, Nav2, and Nrn1 may be involved in the recovery of synaptic structures after interference with KLK6. Collectively, KLK6 participate in the development of CH and might provide new target for the treatment of CH.