Treffer: Custom made python script using network assignment and scoring to estimate the impact of biological processes.

Blood-borne factors are essential to maintain neuronal synaptic plasticity and cognitive resilience throughout life. One such factor is osteocalcin (OCN), a pro-youthful hormone produced by bones, that influences hippocampal neuronal homeostasis. However, the way how this blood-borne factor communicates with neurons remains unclear. Here, we show the importance of a core primary cilium (PC)-protein/autophagy axis in mediating OCN's effects. We found that OCN's receptor, GPR158, is present at the PC of hippocampal neurons and mediates the regulation of autophagy machinery by OCN. During aging, autophagy and PC-core proteins are reduced in neurons and restoring their levels is sufficient to improve cognitive impairments in aged mice. Mechanistically, the induction of this axis by OCN is dependent on the PC-dependent cAMP response element-binding protein signaling pathway. Altogether, this study demonstrates that PC/autophagy axis is a gateway to mediate blood-borne factor-neuron communication and advances our understanding of the mechanism involved in age-related cognitive decline. ; Funding provided by: Agence Nationale de la RechercheROR ID: https://ror.org/00rbzpz17Award Number: ; A custom made python script using network assignment and scoring to estimate the impact of biological processes and pathways in the context of specific functions. The code uses specific biological pathways by enriching them with gene ontologies (KEGG database, Reactome, etc.) and assigning them to nodes and connections, to determine centrality and peripherality of the factors