ArticlePloS one2012
Regulated proteolytic processing of Reelin through interplay of tissue plasminogen activator (tPA), ADAMTS-4, ADAMTS-5, and their modulators.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 88 citations in OpenAlex.
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- Identification of a reactive astrocyte subpopulation during HIV-associated pain pathogenesis in mouse models.Nature communications · 2025Article
- Olfactory ensheathing cells from adult female rats are hybrid glia that promote neural repair.eLife · 2025Article
- Reelin Deficiency and Synaptic Impairment in the Adolescent Prefrontal Cortex Following Initial Synthetic Cannabinoid Exposure.Biological psychiatry global open science · 2025Article
- Regulatory mechanism of Reelin activity: a platform for exploiting Reelin as a therapeutic agent.Frontiers in molecular neuroscience · 2025Review
- De novo monoallelic Reelin missense variants cause dominant neuronal migration disorders via a dominant-negative mechanism.The Journal of clinical investigation · 2024Article
- The Inflammation-Induced Dysregulation of Reelin Homeostasis Hypothesis of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Review
- Reelin Signaling in Neurodevelopmental Disorders and Neurodegenerative Diseases.Brain sciences · 2023Review
- Functional Diversity of Neuronal Cell Adhesion and Recognition Molecule L1CAM through Proteolytic Cleavage.Cells · 2022Review
- Altered Balance of Reelin Proteolytic Fragments in the Cerebrospinal Fluid of Alzheimer's Disease Patients.International journal of molecular sciences · 2022Article
- Considering the Role of Extracellular Matrix Molecules, in Particular Reelin, in Granule Cell Dispersion Related to Temporal Lobe Epilepsy.Frontiers in cell and developmental biology · 2022Review
- Delayed maturation of P2 flash visual evoked potential (VEP) latency in newborns of gestational diabetic mothers.Early human development · 2021Article
- Neuroserpin Is Strongly Expressed in the Developing and Adult Mouse Neocortex but Its Absence Does Not Perturb Cortical Lamination and Synaptic Proteome.Frontiers in neuroanatomy · 2021Article
- Serum Glycoproteomics and Identification of Potential Mechanisms Underlying Alzheimer's Disease.Behavioural neurology · 2021Article
- Poly (ADP-Ribose) Polymerase 1 Regulates Cajal-Retzius Cell Development and Neural Precursor Cell Adhesion.Frontiers in cell and developmental biology · 2021Article
- Reelin Functions, Mechanisms of Action and Signaling Pathways During Brain Development and Maturation.Biomolecules · 2020Review
- Fyn Tyrosine Kinase as Harmonizing Factor in Neuronal Functions and Dysfunctions.International journal of molecular sciences · 2020Review
- New Insights into ADAMTS Metalloproteases in the Central Nervous System.Biomolecules · 2020Review
- ADAMTS-5: A difficult teenager turning 20.International journal of experimental pathology · 2020Review
- Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons.Molecular metabolism · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The extracellular signaling protein Reelin, indispensable for proper neuronal migration and cortical layering during development, is also expressed in the adult brain where it modulates synaptic functions. It has been shown that proteolytic processing of Reelin decreases its signaling activity and promotes Reelin aggregation in vitro, and that proteolytic processing is affected in various neurological disorders, including Alzheimer's disease (AD). However, neither the pathophysiological significance of dysregulated Reelin cleavage, nor the involved proteases and their modulators are known. Here we identified the serine protease tissue plasminogen activator (tPA) and two matrix metalloproteinases, ADAMTS-4 and ADAMTS-5, as Reelin cleaving enzymes. Moreover, we assessed the influence of several endogenous protease inhibitors, including tissue inhibitors of metalloproteinases (TIMPs), α-2-Macroglobulin, and multiple serpins, as well as matrix metalloproteinase 9 (MMP-9) on Reelin cleavage, and described their complex interplay in the regulation of this process. Finally, we could demonstrate that in the murine hippocampus, the expression levels and localization of Reelin proteases largely overlap with that of Reelin. While this pattern remained stable during normal aging, changes in their protein levels coincided with accelerated Reelin aggregation in a mouse model of AD.
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