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Cited by 44Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Netrin-1 receptor UNC5C cleavage by active δ-secretase enhances neurodegeneration, promoting Alzheimer’s disease pathologies

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Chen, Guiqin, Kang, Seong Su, Wang, Zhihao, Ahn, Eun Hee, Xia, Yiyuan, Liu, Xia, Sandoval, Ivette M., Manfredsson, Fredric P. +2 more·2021·Science Advances
DOI 10.1126/sciadv.abe4499PMC PMC8051868
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Abstract

Netrin-1 reduction activates AEP that cleaves UNC5C receptor, contributing to AD pathogenesis.

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Crossref · 10.1126/sciadv.abe4499

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  • δ-Secretase precuts APP, facilitating β-secretase 1 access, and simultaneously cleaves TrkB, tau, and UNC5C, amplifying both Aβ production and tau pathology.

    “For example, δ-Secretase precuts APP, facilitating β-secretase 1 access, and simultaneously cleaves proteins such as tropomyosin receptor kinase B (TrkB), tau, and netrin receptor (UNC5C), amplifying both Aβ production and tau pathology [32].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [32]

    The Introduction and Results report that δ-secretase cleaves APP, tau, and UNC5C, with increased Aβ production and tau-related pathology. The Results identify APP cleavage at N585, but do not say that this gives β-secretase 1 access. The Discussion says cleaved tau binds TrkB and inhibits its signaling; it does not say δ-secretase cleaves TrkB. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Chen, G., Kang, S. S., Wang, Z., Ahn, E. H., Xia, Y., Liu, X., Sandoval, I. M., Manfredsson, F. P., Zhang, Z., & Ye, K.
Affiliations
  • Emory University (US)
  • Barrow Neurological Institute (US)
  • Renmin Hospital of Wuhan University (CN)
Corresponding author
  • Zhang, Zhaohui
  • Ye, Keqiang
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2021-04-16
Volume
7
Issue
16
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.abe4499
PMC
PMC8051868
OpenAlex
W3153292507
Cited by
44
References
3
Citations by year
2026: 1 · 2025: 13 · 2024: 9 · 2023: 12 · 2022: 5 · 2021: 4
FWCI
4.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (AG051538)
  • National Institute of Neurological Disorders and Stroke (P30NS055077)
  • Alzheimer’s Disease Research Center, Emory University (P30 AG066511)
  • National Natural Science Foundation of China (81671051)
  • National Institutes of Health under Award Number (UL1TR002378)
  • National Institute of Health RF1 (AG051538)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
netrin-1, UNC5C, Alzheimer's disease, neurodegeneration, neuronal apoptosis, caspase-3 activation, APP/PS1 mice, learning and memory impairment, axon guidance receptors
MeSH terms
Netrin Receptors, Netrin-1, Alzheimer Disease, Animals, Cell Death, Mice, Amyloid Precursor Protein Secretases

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