ArticleCell reports2015
Antagonistic Effects of BACE1 and APH1B-γ-Secretase Control Axonal Guidance by Regulating Growth Cone Collapse.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease: A Truncated Randomized Phase 2b/3 Clinical Trial.JAMA neurology · 2021Trial
- The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease.EMBO molecular medicine · 2018Trial
- Identification of tryptophan metabolism-related genes in immunity and immunotherapy in Alzheimer's disease.Aging · 2023Article
- Postnatal neuronal Bace1 deletion impairs neuroblast and oligodendrocyte maturation.Human molecular genetics · 2023Article
- The Alzheimer's disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130.Molecular neurodegeneration · 2023Article
- Alzheimer's Disease: An Updated Overview of Its Genetics.International journal of molecular sciences · 2023Review
- Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.Current neuropharmacology · 2023Article
- The BACE1-generated C-terminal fragment of the neural cell adhesion molecule 2 (NCAM2) promotes BACE1 targeting to Rab11-positive endosomes.Cellular and molecular life sciences : CMLS · 2022Article
- γ-secretase promotes Drosophila postsynaptic development through the cleavage of a Wnt receptor.Developmental cell · 2022Article
- Intercellular signaling by ectodomain shedding at the synapse.Trends in neurosciences · 2022Review
- The β-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice.Molecular neurobiology · 2022Article
- Selected Natural Products in Neuroprotective Strategies for Alzheimer's Disease-A Non-Systematic Review.International journal of molecular sciences · 2022Review
- The case for low-level BACE1 inhibition for the prevention of Alzheimer disease.Nature reviews. Neurology · 2021Review
- Roles and Mechanisms of Axon-Guidance Molecules in Alzheimer's Disease.Molecular neurobiology · 2021Review
- Beta-Secretase 1 Underlies Reactive Astrocytes and Endothelial Disruption in Neurodegeneration.Frontiers in cellular neuroscience · 2021Article
- New insights into the molecular mechanisms of axon guidance receptor regulation and signaling.Current topics in developmental biology · 2021Review
- Downregulation of Adhesion Molecule CHL1 in B Cells but Not T Cells of Patients with Major Depression and in the Brain of Mice with Chronic Stress.Neurotoxicity research · 2020Article
- Expression of Genes Involved in Axon Guidance: How Much Have We Learned?International journal of molecular sciences · 2020Review
- Cell Adhesion Molecules Involved in Neurodevelopmental Pathways Implicated in 3p-Deletion Syndrome and Autism Spectrum Disorder.Frontiers in cellular neuroscience · 2020Review
- BACE1 partial deletion induces synaptic plasticity deficit in adult mice.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 5 countries.
Funding
Abstract
ΒACE1 is the major drug target for Alzheimer's disease, but we know surprisingly little about its normal function in the CNS. Here, we show that this protease is critically involved in semaphorin 3A (Sema3A)-mediated axonal guidance processes in thalamic and hippocampal neurons. An active membrane-bound proteolytic CHL1 fragment is generated by BACE1 upon Sema3A binding. This fragment relays the Sema3A signal via ezrin-radixin-moesin (ERM) proteins to the neuronal cytoskeleton. APH1B-γ-secretase-mediated degradation of this fragment stops the Sema3A-induced collapse and sensitizes the growth cone for the next axonal guidance cue. Thus, we reveal a cycle of proteolytic activity underlying growth cone collapse and restoration used by axons to find their correct trajectory in the brain. Our data also suggest that BACE1 and γ-secretase inhibition have physiologically opposite effects in this process, supporting the idea that combination therapy might attenuate some of the side effects associated with these drugs.
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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.