Norbert Weiss

Norbert Weiss
Charles University in Prague | CUNI · Department of Pathophysiology (3. LF)

PhD Neuroscience-Neurobiology
http://www.theweisslab.com

About

101
Publications
90,822
Reads
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1,823
Citations
Additional affiliations
January 2021 - present
Charles University in Prague
Position
  • Group Leader
January 2018 - December 2018
Ulm University
Position
  • Professor
March 2015 - December 2017
Peter the Great St.Petersburg Polytechnic University
Position
  • Professor
Education
September 2003 - December 2006
University Joseph Fourier - Grenoble 1
Field of study
  • Neuroscience / Neurobiology

Publications

Publications (101)
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. In a recent study by Steinberg and colleagues, two recessive missense mutations were identified in the Cav3.2 T-type calcium channel gene (CACNA1H), in a family with an affected proband (early onset, long duratio...
Article
Full-text available
T-type calcium channels are key contributors to neuronal physiology where they shape electrical activity of nerve cells and contribute to the release of neurotransmitters. Enhanced T-type channel expression has been causally linked to a number of pathological conditions including peripheral painful diabetic neuropathy. Recently, it was demonstrated...
Article
Full-text available
Neuronal voltage-gated calcium channels (VGCCs) serve complex yet essential physiological functions via their pivotal role in translating electrical signals into intracellular calcium elevations and associated downstream signaling pathways. There are a number of regulatory mechanisms to ensure a dynamic control of the number of channels embedded in...
Article
Full-text available
Low-voltage-activated T-type calcium channels are essential contributors to the functioning of thalamocortical neurons by supporting burst-firing mode of action potentials. Enhanced T-type calcium conductance has been reported in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and proposed to be causally related to the overall development...
Article
Full-text available
T-type channels are low-voltage-activated calcium channels that contribute to a variety of cellular and physiological functions, including neuronal excitability, hormone and neurotransmitter release as well as developmental aspects. Several human conditions including epilepsy, autism spectrum disorders, schizophrenia, motor neuron disorders and ald...
Article
Full-text available
Blood platelets produced by bone marrow megakaryocytes play a fundamental role in the initiation of endogenous hemostasis and effective endothelial repair following vascular injury. Although most platelets are found circulating inactivated in the intact vasculature, they rapidly become activated on vessel wall injury and adhere to the exposed extra...
Article
Full-text available
Citation: Coquerel, Q.; Legendre, C.; Frangieh, J.; Waard, S.D.; Montnach, J.; Cmarko, L.; Khoury, J.; Hassane, C.S.; Bréard, D.; Siegler, B.; et al. Abstract: Voltage-gated Na + (Na V) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel Na V channel ligands. With...
Article
Full-text available
Voltage‑gated calcium channels are essential regulators of brain function where they support depolarization‑induced calcium entry into neurons. They consist of a pore‑forming subunit (Cavα1) that requires co‑assembly with ancillary subunits to ensure proper functioning of the channel. Among these ancillary subunits, the Cavβ plays an essential role...
Article
Full-text available
Low‐voltage‐activated T‐type Ca2+ channels are key regulators of neuronal excitability both in the central and periph‐ eral nervous systems. Therefore, their recruitment at the plasma membrane is critical in determining firing activity patterns of nerve cells. In this study, we report the importance of secretory carrier‐associated membrane proteins...
Article
Full-text available
In this brief report, we demonstrate that the Cav3.3 T-type voltage-gated calcium channel subtype is involved in our FRICTION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Cav3.3 is significantly upregulated in whole trigeminal ganglia of FRICTION mice compared to controls at week 10 post-injury. We co...
Article
Full-text available
Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies that are characterized by seizures and developmental delay. DEEs are primarily attributed to genetic causes and an increasing number of cases have been correlated with variants in ion channel genes. In this study, we report a child with an early severe DEE. Whole e...
Article
Full-text available
Neuronal voltage-gated calcium channels play a pivotal role in the conversion of electrical signals into calcium entry into nerve endings that is required for the release of neurotransmitters. They are under the control of a number of cellular signaling pathways that serve to fine tune synaptic activities, including G-protein coupled receptors (GPC...
Chapter
Neuronal voltage-gated calcium channels play an essential role for calcium entry into presynaptic endings responsible for the release of neurotransmitters. In turn, and in order to fine-tune synaptic activity, numerous neurotransmitters exert a potent negative feedback over the calcium signal provided by G-protein-coupled receptors that can be reco...
Article
Full-text available
Low-voltage-activated T-type calcium channels are important contributors to nervous system function. Post-transla-tional modification of these channels has emerged as an important mechanism to control channel activity. Previous studies have documented the importance of asparagine (N)-linked glycosylation and identified several asparagine residues w...
Article
Full-text available
Low-voltage-activated Ca v 3 calcium channels (T-type) play an essential role in the functioning of the nervous system where they support oscillatory activities that relie on several channel molecular determinants that shape their unique gating properties. In a previous study, we documented the important role of the carboxy proximal region in the f...
Article
Full-text available
Cav3.2 T-type calcium channels play an essential role in the transmission of peripheral nociception in the dorsal root ganglia (DRG) and alteration of Cav3.2 expression is associated with the development of peripheral painful diabetic neuropathy (PDN). Several studies have previously documented the role of glycosylation in the expression and functi...
Article
Full-text available
Neuropathic pain syndromes affect between 30 and 50% of the world population and represent a significant burden for patients, society, and healthcare systems. Many hypotheses have been formulated about the mechanisms of neuropathic pain among which elevated expression of T-type calcium channels in peripheral nociceptive nerve fibers (so-called “noc...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of cortical, brain stem and spinal motor neurons that leads to muscle weakness and death. A previous study implicated CACNA1H encoding for Cav3.2 calcium channels as a susceptibility gene in ALS. In the present study, two heterozygous CACNA1H v...
Article
Full-text available
Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, usin...
Article
Full-text available
Neuromuscular disorders encompass a wide range of conditions often associated with a genetic component. In the present study, we report a patient with severe infantile-onset amyotrophy in whom two compound heterozygous variants in the gene CACNA1H encoding for Cav3.2 T-type calcium channels were identified. Functional analysis of Cav3.2 variants re...
Article
Full-text available
The physiological functions controlled by T-type channels are intrinsically dependent on their gating properties, and alteration of T-type channel activity is linked to several human disorders. Therefore, it is essential to develop a clear understanding of the structural determinants responsible for the unique gating features of T-type channels. He...
Article
Full-text available
Low-voltage activated T-type calcium channels mediate essential functions in the nervous system, and alteration of channel activity is causally linked to a number of neurological conditions. Therefore, T-type channels hold great promise as pharmacological targets for new medicines. In this Viewpoint, we discuss the potential of T-type channels as d...
Article
Full-text available
Multiple voltage-gated calcium channels (VGCCs) contribute to the processing of nociceptive signals in primary afferent fibers. In addition, alteration of calcium channel activity is associated with a number of chronic pain conditions. Therefore, VGCCs have emerged as prime target for the management of either neuropathic or inflammatory pain, and s...
Article
Full-text available
Recent findings have revealed a fundamental role of the ubiquitin-proteasome system (UPS) in the regulation of voltage-gated Ca2+ channels (VGCCs). It has been proposed that the ubiquitination-deubiquitination balance dictates the number of channels expressed at the plasma membrane, which in turn influences a number of physiological and pathophysio...
Article
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Commentary to: Low-voltage-activated Ca v 3.1 calcium channels shape T helper cell cytokine profiles (Immunity 2016, 782–794) C o m m e n t a r y
Article
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Commentary to: Identification of glycosylation sites essential for surface expression of the Cav α2δ1 subunit and modulation of the cardiac Cav1.2 channel activity (J. Biol. Chem. 2016, pp. 4826-4843)
Article
Full-text available
Low-voltage-activated T-type calcium channels are essential contributors to neuronal physiology where they play complex yet fundamentally important roles in shaping intrinsic excitability of nerve cells and neurotransmission. Aberrant neuronal excitability caused by alteration of T-type channel expression has been linked to a number of neuronal dis...
Chapter
Full-text available
Neuronal voltage-gated calcium channels play an essential role for calcium entry into presynaptic endings responsible for the release of neurotransmitters. In turn, and in order to fine tune synaptic activity, numerous neurotransmitters exert a potent negative feedback over the calcium signal provided by G-protein-coupled receptors that can be reco...
Article
Full-text available
Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. Currently, little is known about the cellular mechanisms controlling th...
Article
Full-text available
Alteration of intracellular calcium (Ca(2+) ) homeostasis has emerged as an underlying mechanism of neurodegenerative diseases (Marambaud et al., 2009). Within neurons, calcium ions (Ca(2+) ) represent an essential signaling molecule, responsible for regulating a large number of diverse cellular functions including membrane excitability, synaptic t...
Article
Full-text available
Fast neurotransmitter release in the central and peripheral nervous system relies on the tight control of Ca2+ influx into presynaptic nerve endings and the synchronized exocytosis of neurotransmitter vesicles. Neuronal voltage-gated Ca2+ channels (VGCCs), especially Cav2.1 and Cav2.2 channels and most likely Cav3 T-type channels, by virtue of thei...
Book
Calcium ions represent Mother Nature’s ‘ion-of-choice’ for regulating fundamental physiological functions, as they initiate a new life at the time of fertilization and guide subsequent developmental and physiological functions of the human body. Calcium channels, which act as gated pathways for the movement of calcium ions across the membranes, pla...
Article
Full-text available
One of the most remarkable features of T-type Ca2+ channels originates from their low-threshold of activation that makes these channels perfectly suited for regulating neuronal excitability and oscillatory behavior near the resting membrane potential of the cells. They generate a low-threshold burst discharge that occur during diverse forms of neur...
Article
Full-text available
In mammalian skeletal muscle, contraction is triggered by the excitation-contraction (E-C) coupling machinery local- ized at the triad, a specialized membrane structure formed by the juxtaposition of T-tubules and sarcoplasmic reticulum (SR) cisternae. E-C coupling relies on a tight control of SR Ca2+ release through the type-1 ryanodine receptor (...
Article
Full-text available
Commentary to: Functional changes in pyramidal neurons in the chronic methamphetamine-treated rat. (Gen. Physiol. Biophys. 2015, pp.5-12).
Article
Full-text available
Neuronal voltage-gated calcium channels have evolved as one of the most important players for calcium entry into presynaptic endings responsible for the release of neurotransmitter. In turn, and in order to fine tune synaptic activity and neuronal communication, numerous neurotransmitters exert a potent negative autocrine and/or paracrine control o...
Article
Full-text available
Ion channels play a crucial role in cell functioning, contributing to transmembrane potential and participating in cell signalling and homeostasis. To fulfil highly specialised functions, cells have developed various mechanisms to regulate channel expression and activity at particular subcellular loci, and alteration of ion channel regulation can l...
Article
T-type calcium channels are essential contributors to the transmission of nociceptive signals in the primary afferent pain pathway. Here, we show that T-type calcium channels are ubiquitinated by WWP1, a plasma-membrane-associated ubiquitin ligase that binds to the intracellular domain III-IV linker region of the Cav3.2 T-type channel and modifies...
Article
Full-text available
Neuronal abnormalities in neurodegenerative disorders such as Huntington disease, Alzheimer disease or Parkinson disease have been the primary focus of decades of research. However, increasing evidences indicate that glial cells and more specifically astrocytes could be as important players as their big brother. It is now particularly evident in Hu...
Patent
The invention provides methods treating pain by inhibiting a Cav3.2 channel expression or function, including the use of contacting said channel in situ with an inhibitor of USP5 or an inhibitor of the interaction between Cav3.2 and USP5.
Article
Full-text available
Perhaps one of the most remarkable features of T-type calcium channels is their low-threshold of activation that makes these channels important candidates for calcium entry near the resting membrane potential of neurons. Hence, they mediate low-threshold burst discharges that occur during different forms of neuronal rhythmogenesis, but play also im...
Book
Full-text available
Calcium ions represent Mother Nature’s ‘ion-of-choice’ for regulating fundamental physiological functions, as they initiate a new life at the time of fertilization and guide subsequent developmental and physiological functions of the human body. Calcium channels, which act as gated pathways for the movement of calcium ions across the membranes, pla...
Conference Paper
Full-text available
Low-voltage-activated T-type calcium channels play important roles in neuronal physiology where they control cellular excitabil- ity and synaptic transmission. Alteration in T-type channel expression has been linked to various pathophysiological condi- tions such as pain arising from diabetic neuropathy. In the pres- ent study, we looked at the rol...
Chapter
Full-text available
Voltage-gated Ca2+ channels represent one of the main pathways for Ca2+ entry into nerve terminals where they play a critical role in the control of synaptic exocytosis. It is traditionally believed that the vesicle-docking/release machinery must be located in the vicinity of the calcium source in order to trigger fast, efficient and spatially deli...
Article
Full-text available
Low-voltage-activated T-type calcium channels play important roles in neuronal physiology where they control cellular excitability and synaptic transmission. Alteration in T-type channel expression has been linked to various pathophysiological conditions such as pain arising from diabetic neuropathy. In the present study, we looked at the role of a...
Article
Full-text available
Neurodegenerative diseases are a burden of our century. Although significant efforts were made to find a cure or relief to this scourge, their pathophysiology remains vague and the cellular function of the key involved proteins is still unclear. However, in the case of amyloid β (Aβ), a key protein concerned in Alzheimer disease, we are now a step...
Article
Full-text available
Low-voltage-activated (LVA) T-type Ca(2+) channels differ from their high-voltage-activated (HVA) homologues by unique biophysical properties. Hence, whereas HVA channels convert action potentials into intracellular Ca(2+) elevations, T-type channels control Ca(2+) entry during small depolarizations around the resting membrane potential. They play...
Article
Full-text available
To date, nearly 35.6 million people world wide live with dementia, and the situation is going to get worse by 2050 with 115.4 million cases.1 In the western world, the prevalence for dementia in people over the age of 60 is greater than 5% and two thirds are due to Alzheimer disease,2-5 the most common form of dementias. Alzheimer disease (AD), fi...
Article
Full-text available
Low-voltage-activated T-type calcium channels act as a major pathway for calcium entry near the resting membrane potential in a wide range of neuronal cell types. Several reports have uncovered an unrecognized feature of T-type channels in the control of vesicular neurotransmitter and hormone release, a process so far thought to be mediated exclusi...
Article
Full-text available
The use of ion channels to control defined events in defined cell types at defined times in the context of living tissue or whole organism represent one of the major advance of the last decade, and optogenetics (i.e the combination of genetic and optical methods) obviously played a key role in this achievement.(1) Although the existence of light-ac...
Article
Full-text available
Described by the Belgian cytologist Christian De Duve in 1949,11. de Duve C. The lysosome turns fifty. Nat Cell Biol 2005; 7:847 - 9; http://dx.doi.org/10.1038/ncb0905-847; PMID: 16136179 [CrossRef]View all references lysosomes (from the Greek “digestive bodies”) are ubiquitous specialized intracellular organelles that ensure the degradation/recycl...
Chapter
Full-text available
Calcium entry through neuronal voltage-gated calcium channels into presynaptic nerve terminal is a key step in synaptic exocytosis. In order to receive the calcium signal and trigger fast, efficient and spatially delimited neurotransmitter release, the vesicle-docking/release machinery must be located near the calcium source. In many cases, this cl...
Article
Full-text available
T-type calcium channels represent a key pathway for Ca2+ entry near the resting membrane potential. Increasing evidence supports a unique role of these channels in fast and low-threshold exocytosis in an action potential-independent manner, but the underlying molecular mechanisms have remained unknown. Here, we report the existence of a syntaxin-1A...
Article
Full-text available
T-type calcium channels represent a key pathway for Ca(2+) entry near the resting membrane potential. Increasing evidence supports a unique role of these channels in fast and low-threshold exocytosis in an action potential-independent manner, but the underlying molecular mechanisms have remained unknown. Here, we report the existence of a syntaxin-...
Article
Full-text available
Regulation of presynaptic voltage-gated calcium channels is critical for depolarization-evoked neurotransmitter release. Various studies attempted to determine the functional implication of Rim1, a component of the vesicle release machinery. Besides to couple voltage-gated Ca(2+) channels to the presynaptic vesicle release machinery, it was evidenc...
Article
Full-text available
 Nauclea latifolia Smith (Rubiaceae) is a small tree found in tropical areas in Africa. It is used in traditional medicine to treat malaria, epilepsy, anxiety, pain, fever, etc. Objective: The aim of this study was to investigate the effects of Nauclea latifolia roots decoction on the peripheral and central nervous systems and its possible mechanis...
Article
Full-text available
Commentary on: Research Paper CaV2.1 (P/Q channel) interaction with synaptic proteins is essential for depolarization-evoked release by Moshe Cohen-Kutner, Daphna Nachmanni and Daphne AtlasVolume 4, Issue 4
Article
A number of G-protein-coupled receptors are expressed in skeletal muscle but their roles in muscle physiology and downstream effector systems remain poorly investigated. Here we explored the functional importance of the G-protein betagamma (Gbetagamma) signalling pathway on voltage-controlled Ca(2+) homeostasis in single isolated adult skeletal mus...