ArticleJournal of neurochemistry2020
Peptidase neurolysin functions to preserve the brain after ischemic stroke in male mice.
Article in Journal of neurochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Structural and functional dissection of human neurolysin through alanine-scanning mutagenesis.The FEBS journal · 2026Article
- Discovery of a pyridine-piperazine-based small molecule that enhances the activity of peptidase neurolysin.The Journal of pharmacology and experimental therapeutics · 2026Article
- Conformation Driven Enhancement of Neurolysin Activity in Presence of a Small Molecule Activator.bioRxiv : the preprint server for biology · 2026Article
- Development of a deep learning-based grid walking test for assessing post-stroke motor function in mice.Frontiers in behavioral neuroscience · 2026Article
- Decoding mechanisms and protein markers in lung-brain axis.Respiratory research · 2025Review
- The Missing Enzymes: A Call to Update Pharmacological Profiling Practices for Better Drug Safety Assessment.Journal of medicinal chemistry · 2025Review
- Structural basis of divergent substrate recognition and inhibition of human neurolysin.Scientific reports · 2024Article
- The utility of serum glucose potassium ratio as a predictive factor for haemorrhagic transformation, stroke recurrence, and mortality among ischemic stroke patients.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Imidazole Bioisostere Activators of Endopeptidase Neurolysin with Enhanced Potency and Metabolic Stability.ACS medicinal chemistry letters · 2024Article
- Gene therapy of adeno-associated virus (AAV) vectors in preclinical models of ischemic stroke.CNS neuroscience & therapeutics · 2023Review
- Discovery of the Next Generation of Non-peptidomimetic Neurolysin Activators with High Blood-Brain Barrier Permeability: a Pharmacokinetics Study in Healthy and Stroke Animals.Pharmaceutical research · 2023Article
- Is Diminazene an Angiotensin-Converting Enzyme 2 (ACE2) Activator? Experimental Evidence and Implications.The Journal of pharmacology and experimental therapeutics · 2022Article
- Small molecule neurolysin activators, potential multi-mechanism agents for ischemic stroke therapy.Expert opinion on therapeutic targets · 2022Article
- The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke.Neuromolecular medicine · 2021Article
- Identification and Characterization of Two Structurally Related Dipeptides that Enhance Catalytic Efficiency of Neurolysin.The Journal of pharmacology and experimental therapeutics · 2021Article
- Discovery of First-in-Class Peptidomimetic Neurolysin Activators Possessing Enhanced Brain Penetration and Stability.Journal of medicinal chemistry · 2021Article
- Delayed atomoxetine or fluoxetine treatment coupled with limited voluntary running promotes motor recovery in mice after ischemic stroke.Neural regeneration research · 2021Article
- Delayed Exercise-induced Upregulation of Angiogenic Proteins and Recovery of Motor Function after Photothrombotic Stroke in Mice.Neuroscience · 2021Article
- Between two storms, vasoactive peptides or bradykinin underlie severity of COVID-19?Physiological reports · 2021Review
- Neurolysin substrates bradykinin, neurotensin and substance P enhance brain microvascular permeability in a human in vitro model.Journal of neuroendocrinology · 2021Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Previous studies documented up-regulation of peptidase neurolysin (Nln) after brain ischemia, however, the significance of Nln function in the post-stroke brain remained unknown. The aim of this study was to assess the functional role of Nln in the brain after ischemic stroke. Administration of a specific Nln inhibitor Agaricoglyceride A (AgaA) to mice after stroke in a middle cerebral artery occlusion model, dose-dependently aggravated injury measured by increased infarct and edema volumes, blood-brain barrier disruption, increased levels of interleukin 6 and monocyte chemoattractant protein-1, neurological and motor deficit 24 h after stroke. In this setting, AgaA resulted in inhibition of Nln in the ischemic hemisphere leading to increased levels of Nln substrates bradykinin, neurotensin, and substance P. AgaA lacked effects on several physiological parameters and appeared non-toxic to mice. In a reverse approach, we developed an adeno-associated viral vector (AAV2/5-CAG-Nln) to overexpress Nln in the mouse brain. Applicability of AAV2/5-CAG-Nln to transduce catalytically active Nln was confirmed in primary neurons and in vivo. Over-expression of Nln in the mouse brain was also accompanied by decreased levels of its substrates. Two weeks after in vivo transduction of Nln using the AAV vector, mice were subjected to middle cerebral artery occlusion and the same outcome measures were evaluated 72 h later. These experiments revealed that abundance of Nln in the brain protects animals from stroke. This study is the first to document functional significance of Nln in pathophysiology of stroke and provide evidence that Nln is an endogenous mechanism functioning to preserve the brain from ischemic injury.
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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.