Immunocytoprotection after reperfusion with Kv1.3 inhibitors has an extended treatment window for ischemic stroke

Article Medicine, Research & Experimental

A Biodistribution Study of the Radiolabeled Kv1.3-Blocking Peptide DOTA-HsTX1[R14A] Demonstrates Brain Uptake in a Mouse Model of Neuroinflammation

Sanjeevini Babu Reddiar et al.

Summary: This study investigates the in vivo distribution of HsTX1[R14A] peptide in mice and finds increased uptake in a LPS-induced mouse model of neuroinflammation, as well as accumulation in inflamed joints.

MOLECULAR PHARMACEUTICS (2023)

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Article Clinical Neurology

Reperfusion Injury Is Associated With Poor Outcome in Patients With Recanalization After Thrombectomy

Ying Zhou et al.

Summary: This study aimed to investigate the presence of reperfusion injury in acute ischemic stroke patients with recanalization after mechanical thrombectomy and analyze its impact on neurological outcome. The results showed that reperfusion injury was relatively frequent in stroke patients with recanalization after mechanical thrombectomy and was associated with poor prognosis.

STROKE (2023)

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Article Immunology

Blocking P2X7 by intracerebroventricular injection of P2X7-specific nanobodies reduces stroke lesions

Maximilian Wilmes et al.

Summary: The study demonstrates that blocking P2X7 channel can attenuate the inflammatory response in brain diseases. The newly developed P2X7-specific nanobodies effectively target this channel. Intracerebroventricular injection of P2X7-specific nanobodies reduces the size of stroke.

JOURNAL OF NEUROINFLAMMATION (2022)

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Article Pharmacology & Pharmacy

Effective targeting of microglial P2X7 following intracerebroventricular delivery of nanobodies and nanobody-encoding AAVs

Carolina Pinto-Espinoza et al.

Summary: This study evaluated the ability of P2X7-specific nanobodies to reach and block P2X7 on microglia. The results showed that intracerebral injection of nanobodies achieved faster and more effective blockade of microglial P2X7 compared to intravenous injection. Additionally, the endogenous production of nanobody-encoding AAVs resulted in long-term occupancy and blockade of P2X7 on microglia.

FRONTIERS IN PHARMACOLOGY (2022)

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Review Immunology

The role of T cells in age-related diseases

Elisa Carrasco et al.

Summary: T cells play a crucial role in age-related diseases, potentially leading to the failure of immune tolerance mechanisms and tissue damage. Targeting T cells could offer new therapeutic opportunities to enhance resilience to age-related diseases.

NATURE REVIEWS IMMUNOLOGY (2022)

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Review Biochemistry & Molecular Biology

Kv1.3 inhibition attenuates neuroinflammation through disruption of microglial calcium signaling

Alla F. Fomina et al.

Summary: In the past 5 years, inhibitors of the potassium channel K(V)1.3 have been shown to reduce neuroinflammation in various disease models by reducing microglia activation and suppressing pro-inflammatory cytokines and nitric oxide production. Recent studies have revealed that K(V)1.3 channels not only regulate membrane potential, but also play a crucial role in regulating calcium influx in microglia, similar to their role in T cells.

CHANNELS (2021)

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Article Multidisciplinary Sciences

Unique molecular characteristics and microglial origin of Kv1.3 channel-positive brain myeloid cells in Alzheimer's disease

Supriya Ramesha et al.

Summary: By studying Kv1.3-expressing CNS-MPs in AD mouse models, researchers have identified unique molecular features of these cells and confirmed their microglial origin. Blocking Kv1.3 channels in vivo resulted in reduced Aβ burden, increased anti-inflammatory CNS-MPs, and a prophagocytic phenotype in AD mouse models.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Pharmacology & Pharmacy

Lipopolysaccharide influences the plasma and brain pharmacokinetics of subcutaneously-administered HsTX1[R14A], a KV1.3-blocking peptide

Sanjeevini Babu Reddiar et al.

Summary: HsTX1[R14A], a potent and selective peptide blocker of K(V)1.3, showed substantial brain uptake potentially through disruption of brain inter-endothelial tight junctions. This suggests that HsTX1[R14A] may reach microglia in sufficient concentrations to block K(V)1.3 in neuroinflammatory conditions, potentially reducing neurodegenerative diseases.

TOXICON (2021)

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Article Clinical Neurology

The potassium channel Kv1.3 as a therapeutic target for immunocytoprotection after reperfusion

Yi-Je Chen et al.

Summary: The study demonstrates that Kv1.3 gene deletion does not significantly benefit young females, but improves stroke outcomes in young males, old males, and old females. Delayed PAP-1 treatment is beneficial in both young and old females, with Kv1.3 deletion and PAP-1 treatment significantly reducing microglia/macrophage activation and T-cell infiltration in the ipsilateral hemisphere of old females.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2021)

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Article Gastroenterology & Hepatology

Suppressing Kv1.3 Ion Channel Activity with a Novel Small Molecule Inhibitor Ameliorates Inflammation in a Humanised Mouse Model of Ulcerative Colitis

Anna-Lena Unterweger et al.

Summary: Kv1.3 expression was elevated in UC patients and correlated with the prevalence of TH1 and TH2 T cells. DES1 demonstrated significant anti-inflammatory effects in the treatment of UC, comparable to infliximab or tofacitinib.

JOURNAL OF CROHNS & COLITIS (2021)

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Article Neurosciences

Biophysical basis for Kv1.3 regulation of membrane potential changes induced byP2X4-mediated calcium entry in microglia

Hai M. Nguyen et al.

GLIA (2020)

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Article Medicine, Research & Experimental

Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson's disease

Souvarish Sarkar et al.

JOURNAL OF CLINICAL INVESTIGATION (2020)

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Article Clinical Neurology

Inhibition of the potassium channel Kv1.3 reduces infarction and inflammation in ischemic stroke

Yi-Je Chen et al.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2018)

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Article Neurosciences

Evaluation of reference genes for gene expression studies in mouse and N2a cell ischemic stroke models using quantitative real-time PCR

Yingbo Kang et al.

BMC NEUROSCIENCE (2018)

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Article Medicine, General & Internal

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct

R. G. Nogueira et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Article Clinical Neurology

Kv1.3 inhibition as a potential microglia-targeted therapy for Alzheimer's disease: preclinical proof of concept

Izumi Maezawa et al.

BRAIN (2018)

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Review Endocrinology & Metabolism

The IMPROVE Guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

Nathalie Percie du Sert et al.

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM (2017)

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Article Immunology

A systems pharmacology-based approach to identify novel Kv1.3 channel-dependent mechanisms in microglial activation

Srikant Rangaraju et al.

JOURNAL OF NEUROINFLAMMATION (2017)

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Article Clinical Neurology

Reconsidering Neuroprotection in the Reperfusion Era

Sean I. Savitz et al.

STROKE (2017)

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Article Clinical Neurology

Cytoprotective Drug-Tissue Plasminogen Activator Protease Interaction Assays: Screening of Two Novel Cytoprotective Chromones

Paul A. Lapchak et al.

TRANSLATIONAL STROKE RESEARCH (2017)

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Editorial Material Clinical Neurology

Brief History of Endovascular Acute Ischemic Stroke Treatment

Wade S. Smith et al.

STROKE (2016)

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Article Medicine, General & Internal

Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis

Jeffrey L. Saver et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2016)

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Article Medicine, General & Internal

Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials

Mayank Goyal et al.

LANCET (2016)

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Review Clinical Neurology

The inflammatory penumbra'' in ischemic stroke: From clinical data to experimental evidence

Maxime Gauberti et al.

EUROPEAN STROKE JOURNAL (2016)

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Review Immunology

Ion Channels in Innate and Adaptive Immunity

Stefan Feske et al.

ANNUAL REVIEW OF IMMUNOLOGY VOL 33 (2015)

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Article Chemistry, Medicinal

Development of Highly Selective Kv1.3-Blocking Peptides Based on the Sea Anemone Peptide ShK

Michael W. Pennington et al.

MARINE DRUGS (2015)

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Article Medicine, General & Internal

Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke

M. Goyal et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

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Article Medicine, General & Internal

Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection

B. C. V. Campbell et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

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Article Immunology

Kv1.3 in psoriatic disease: PAP-1, a small molecule inhibitor of Kv1.3 is effective in the SCID mouse psoriasis - Xenograft model

Smriti Kundu-Raychaudhuri et al.

JOURNAL OF AUTOIMMUNITY (2014)

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Review Clinical Neurology

The immunology of acute stroke

Angel Chamorro et al.

NATURE REVIEWS NEUROLOGY (2012)

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Article Clinical Neurology

Microglia/Macrophage Polarization Dynamics Reveal Novel Mechanism of Injury Expansion After Focal Cerebral Ischemia

Xiaoming Hu et al.

STROKE (2012)

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Article Pharmacology & Pharmacy

Durable Pharmacological Responses from the Peptide ShK-186, a Specific Kv1.3 Channel Inhibitor That Suppresses T Cell Mediators of Autoimmune Disease

Eric J. Tarcha et al.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2012)

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Review Biochemistry & Molecular Biology

The immunology of stroke: from mechanisms to translation

Costantino Iadecola et al.

NATURE MEDICINE (2011)

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Review Endocrinology & Metabolism

Statistics in experimental cerebrovascular research: comparison of more than two groups with a continuous outcome variable

Peter Schlattmann et al.

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM (2010)

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Review Clinical Neurology

Microglia in ischemic brain injury

Jonathan R. Weinstein et al.

FUTURE NEUROLOGY (2010)

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Article Medicine, Research & Experimental

Pharmacokinetics, toxicity, and functional studies of the selective kv1.3 channel blocker 5-(4-Phenoxybutoxy)Psoralen in rhesus Macaques

L. E. Pereira et al.

EXPERIMENTAL BIOLOGY AND MEDICINE (2007)

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Article Multidisciplinary Sciences

Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases

Christine Beeton et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2006)

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Article Pharmacology & Pharmacy

Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases

A Schmitz et al.

MOLECULAR PHARMACOLOGY (2005)

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Article Multidisciplinary Sciences

The voltage-gated potassium channel Kv1.3 is highly expressed on inflammatory infiltrates in multiple sclerosis brain

H Rus et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

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Article Clinical Neurology

Flow cytometric analysis of inflammatory cells in ischemic rat brain

M Campanella et al.

STROKE (2002)

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Article Biotechnology & Applied Microbiology

Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes

Jo Vandesompele et al.

GENOME BIOLOGY (2002)

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Immunocytoprotection after reperfusion with Kv1.3 inhibitors has an extended treatment window for ischemic stroke

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