ArticleProceedings of the National Academy of Sciences of the United States of America2020
Netrin1 deficiency activates MST1 via UNC5B receptor, promoting dopaminergic apoptosis in Parkinson's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations.Aging cell · 2022Pooled it
- Hippo-YAP/TAZ signalling at the crossroads of brain ageing and neurological disorders: mechanisms, crosstalk, and therapeutic prospects.Biogerontology · 2026Review
- Experimental model of ventilator-induced lung injury induces proteomic signatures of neurodegeneration in the hippocampus.Intensive care medicine experimental · 2026Article
- Roles and therapeutic prospects of the laminin family in disorders of the nervous system.Journal of translational medicine · 2026Review
- Endothelial UNC5B regulates blood‑retinal barrier homeostasis.International journal of molecular medicine · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- Peptides whose levels change during the attack period in episodic migraine: NETRIN-1 and amylin.Frontiers in neurology · 2026Article
- Sex-dimorphic reprogramming of fetal mouse brain development by maternal estradiol excess.Biology of sex differences · 2025Article
- Insulin-degrading enzyme confers neuroprotection in Parkinson's disease by inhibiting the Hippo signaling pathway.Cell death & disease · 2025Article
- BAP31 represses endoplasmic reticulum stress-mediated apoptosis and alleviates neurodegeneration in Parkinson's disease.Cell death & disease · 2025Article
- The Hippo signaling pathway as a therapeutic target in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Direction and modality of transcription changes caused by TAD boundary disruption in Slc29a3/Unc5b locus depends on tissue-specific epigenetic context.Epigenetics & chromatin · 2025Article
- Netrin-1 signaling pathway mechanisms in neurodegenerative diseases.Neural regeneration research · 2025Article
- Article
- Netrin-1: Dual Roles in Neuroinflammation and Neurodegenerative Disease Dynamics.International journal of inflammation · 2025Review
- Circulating blood circular RNA in Parkinson's Disease; from involvement in pathology to diagnostic tools in at-risk individuals.NPJ Parkinson's disease · 2024Article
- Association between plasma Netrin-1 levels and motor and nonmotor symptoms in Parkinson's disease.CNS neuroscience & therapeutics · 2024Article
- Integration of estimated regional gene expression with neuroimaging and clinical phenotypes at biobank scale.PLoS biology · 2024Article
- IER3IP1-mutations cause microcephaly by selective inhibition of ER-Golgi transport.Cellular and molecular life sciences : CMLS · 2024Article
- Circulating blood circular RNA in Parkinson's Disease; a systematic study.medRxiv : the preprint server for health sciences · 2024Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The Hippo (MST1/2) pathway plays a critical role in restricting tissue growth in adults and modulating cell proliferation, differentiation, and migration in developing organs. Netrin1, a secreted laminin-related protein, is essential for nervous system development. However, the mechanisms underlying MST1 regulation by the extrinsic signals remain unclear. Here, we demonstrate that Netrin1 reduction in Parkinson's disease (PD) activates MST1, which selectively binds and phosphorylates netrin receptor UNC5B on T428 residue, promoting its apoptotic activation and dopaminergic neuronal loss. Netrin1 deprivation stimulates MST1 activation and interaction with UNC5B, diminishing YAP levels and escalating cell deaths. Knockout of UNC5B abolishes netrin depletion-induced dopaminergic loss, whereas blockade of MST1 phosphorylating UNC5B suppresses neuronal apoptosis. Remarkably, Netrin1 is reduced in PD patient brains, associated with MST1 activation and UNC5B T428 phosphorylation, which is accompanied by YAP reduction and apoptotic activation. Hence, Netrin1 regulates Hippo (MST1) pathway in dopaminergic neuronal loss in PD via UNC5B receptor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.