ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
UNC5C Receptor Proteolytic Cleavage by Active AEP Promotes Dopaminergic Neuronal Degeneration in Parkinson's Disease.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Role of Netrin-1 dysregulation in early neuronal pathology of α-synuclein models of Parkinson's disease.Journal of advanced research · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- The impact of blood MCP-1 levels on Alzheimer's disease with genetic variation at the NAV3 and UNC5C loci.Translational psychiatry · 2025Article
- Salivary Proteome Profile of Xerostomic Patients Reveals Pathway Dysregulation Related to Neurodegenerative Diseases: A Pilot Study.International journal of molecular sciences · 2025Article
- Repurposing the memory-promoting meclofenoxate hydrochloride as a treatment for Parkinson's disease through integrative multi-omics analysis.NPJ Parkinson's disease · 2025Article
- The UNC5C T835M mutation associated with Alzheimer's disease leads to neurodegeneration involving oxidative stress and hippocampal atrophy in aged mice.Molecular neurodegeneration · 2025Article
- Alpha-synuclein Fibrils Inhibit Activation of the BDNF/ERK Signaling Loop in the mPFC to Induce Parkinson's Disease-like Alterations with Depression.Neuroscience bulletin · 2025Article
- Netrin-1 signaling pathway mechanisms in neurodegenerative diseases.Neural regeneration research · 2025Article
- Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances.Signal transduction and targeted therapy · 2025Review
- Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Sox6 and ALDH1A1 Truncation by Asparagine Endopeptidase Defines Selective Neuronal Vulnerability in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons.Journal of translational medicine · 2024Article
- Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer's Disease and Other Tauopathies.Molecular neurobiology · 2024Review
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- C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis.Neuroscience bulletin · 2023Review
- The Asparaginyl Endopeptidase Legumain: An Emerging Therapeutic Target and Potential Biomarker for Alzheimer's Disease.International journal of molecular sciences · 2022Review
- UNC5C Receptor Proteolytic Cleavage by Active AEP Promotes Dopaminergic Neuronal Degeneration in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Netrin-1: A Serum Marker Predicting Cognitive Impairment after Spinal Cord Injury.Disease markers · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Netrin-1 is a chemotropic cue mediating axon growth and neural migration in neuronal development, and its receptors deletion in colorectal cancer and UNC5s act as dependence receptors regulating neuronal apoptosis. Asparagine endopeptidase (AEP) is an age-dependent protease that cuts human alpha-synuclein (α-Syn) at N103 and triggers its aggregation and neurotoxicity. In the current study, it is reported that UNC5C receptor is cleaved by AEP in Parkinson's disease (PD) and facilitates dopaminergic neuronal loss. UNC5C is truncated by active AEP in human α-SNCA transgenic mice in an age-dependent manner or induced by neurotoxin rotenone. Moreover, UNC5C is fragmented by AEP in PD brains, inversely correlated with reduced netrin-1 levels. Netrin-1 deprivation in primary cultures induces AEP and caspase-3 activation, triggering UNC5C proteolytic fragmentation and enhancing neuronal loss. Noticeably, blocking UNC5C cleavage by AEP attenuates netrin-1 deprivation-elicited neuronal death and motor disorders in netrin flox/flox mice. Overexpression of AEP-truncated UNC5C intracellular fragment strongly elicits α-Syn aggregation and dopaminergic loss, locomotor deficits in α-SNCA transgenic mice. Hence, the findings demonstrate that netrin-1 reduction and UNC5C truncation by AEP contribute to PD pathogenesis.
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