PXD056975-1

PXD056975 is an original dataset announced via ProteomeXchange.

Title	Primary Cilia-Autophagy Axis in Hippocampal Neurons Is Essential to Maintain Cognitive Fitness
Description	A central hallmark of brain aging is the alteration of neuronal functions in the hippocampus, leading to a progressive decline in learning and memory. Multiple reports have shown the importance of blood-borne factors in inter-tissue communication for the maintenance of cognitive fitness and proper regulation of neuronal homeostasis throughout life. Among these blood-borne factors, we identified Osteocalcin (OCN), a bone-derived hormone. OCN induces autophagy machinery in hippocampal neurons which is essential for activity-dependent synaptic plasticity. However, the way in which blood-borne factors like OCN communicate with neurons, including their regulatory mechanisms, remains largely elusive. Here, we show the importance of a core primary cilium (PC)-proteins/autophagy machinery axis in hippocampal neurons that mediate the effects of the pro-youthful blood factor OCN on neuronal homeostasis and cognitive fitness. 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, PC-core proteins are reduced in hippocampal neurons and associated with neuronal PC morphological abnormalities. Restoring their levels is sufficient to improve neuronal autophagy and cognitive impairments in aged mice. Mechanistically, we found that OCN promotes neuronal autophagy in the hippocampus by the induction of PC-dependent cAMP response element-binding protein (CREB) signaling pathway. Altogether, this study proposes a novel paradigm for blood factor-neuron communication dependent on a neuronal PC/autophagy axis by identifying a novel regulatory pathway fostering cognitive fitness and providing the foundation for autophagy-based therapeutic strategies to treat age-related cognitive dysfunction.
HostingRepository	PRIDE
AnnounceDate	2024-11-07
AnnouncementXML	Submission_2024-11-07_02:26:29.144.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Franck Oury
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-19 18:19:27	ID requested
⏵ 1	2024-11-07 02:26:29	announced

Dataset with its publication pending

submitter keyword: Autophagy, Age-related cognitive dysfunction, Synaptic plasticity,Hippocampus, Primary cilium (PC), Osteocalcin (OCN)

Franck Oury
contact affiliation	Institut Necker Enfants Malades
contact email	franck.oury@inserm.fr
lab head
Franck Oury
contact affiliation	Institut Necker Enfants Malades
contact email	franck.oury@inserm.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/11/PXD056975

PRIDE project URI

• PRIDE
  1. PXD056975
     1. Label: PRIDE project
     2. Name: Primary Cilia-Autophagy Axis in Hippocampal Neurons Is Essential to Maintain Cognitive Fitness