Kv1.3 in the spotlight for treating immune diseases DOI
María Navarro‐Pérez, Jesusa Capera, Anna Benavente-Garcia

et al.

Expert Opinion on Therapeutic Targets, Journal Year: 2024, Volume and Issue: 28(1-2), P. 67 - 82

Published: Feb. 1, 2024

Introduction Kv1.3 is the main voltage-gated potassium channel of leukocytes from both innate and adaptive immune systems. Channel function required for common processes such as Ca2+ signaling but also cell-specific events. In this context, alterations in are associated with multiple disorders. Excessive activity correlates numerous autoimmune diseases, while reduced currents result increased cancer prevalence immunodeficiencies.

Language: Английский

The potential convergence of NLRP3 inflammasome, potassium, and dopamine mechanisms in Parkinson’s disease DOI Creative Commons
Adrianne F. Pike, Ildikò Szabó, Robert Veerhuis

et al.

npj Parkinson s Disease, Journal Year: 2022, Volume and Issue: 8(1)

Published: March 24, 2022

Abstract The pathology of Parkinson’s disease (PD) is characterized by α-synuclein aggregation, microglia-mediated neuroinflammation, and dopaminergic neurodegeneration in the substantia nigra with collateral striatal dopamine signaling deficiency. Microglial NLRP3 inflammasome activation has been linked independently to each these facets PD pathology. voltage-gated potassium channel Kv1.3, upregulated microglia facilitating efflux, also identified as a modulator neuroinflammation models PD. Evidence increasingly suggests that microglial Kv1.3 mechanistically coupled activation, which contingent on efflux. Potassium conductance influences release from midbrain neurons. Dopamine, turn, shown inhibit microglia. In this review, we provide literature framework for hypothesis activity-induced evoked stimuli such α-synuclein, could lead utilizing adjacent neurons counteract process fend off an activated state. If case, sufficient supply would ensure remain under control, but gradually siphoned demand, activity progressively intensify promote three major pathology: neurodegeneration. Risk factors overlapping varying degrees render brain regions susceptible mechanism include high density microglia, initially dopamine, poor insulation myelin.

Language: Английский

Citations

32
STAT4 targets KISS1 to inhibit the oxidative damage, inflammation and neuronal apoptosis in experimental PD models by inactivating the MAPK pathway DOI
Xiaolei Zhang, Yu Wang,

Jia Lv

et al.

Neurochemistry International, Journal Year: 2024, Volume and Issue: 175, P. 105683 - 105683

Published: Feb. 8, 2024

Language: Английский

Citations

8
Proximity Labeling Proteomics Reveals Kv1.3 Potassium Channel Immune Interactors in Microglia DOI Creative Commons
Christine A Bowen, Hai M. Nguyen,

Young Lin

et al.

Molecular & Cellular Proteomics, Journal Year: 2024, Volume and Issue: 23(8), P. 100809 - 100809

Published: June 25, 2024

Language: Английский

Citations

8
The voltage-gated potassium channel KV1.3 as a therapeutic target for venom-derived peptides DOI
Gábor Tajti, Dorothy C.C. Wai, György Panyi

et al.

Biochemical Pharmacology, Journal Year: 2020, Volume and Issue: 181, P. 114146 - 114146

Published: July 9, 2020

Language: Английский

Citations

47
The voltage-gated potassium channel KV1.3 regulates neutrophil recruitment during inflammation DOI Creative Commons
Roland Immler, Wiebke Nadolni,

Annika Bertsch

et al.

Cardiovascular Research, Journal Year: 2021, Volume and Issue: 118(5), P. 1289 - 1302

Published: April 21, 2021

Abstract Aims Neutrophil trafficking within the vasculature strongly relies on intracellular calcium signalling. Sustained Ca2+ influx into cell requires a compensatory efflux of potassium to maintain membrane potential. Here, we aimed investigate whether voltage-gated channel KV1.3 regulates neutrophil function during acute inflammatory process by affecting sustained Methods and results Using in vitro assays electrophysiological techniques, show that is functionally expressed human neutrophils regulating store-operated entry through potential stabilizing K+ efflux. Inhibition specific inhibitor 5-(4-Phenoxybutoxy)psoralen (PAP-1) impaired signalling, thereby preventing cellular spreading, adhesion strengthening, appropriate crawling under flow conditions vitro. intravital microscopy, pharmacological blockade or genetic deletion mice decreased blood dependent fashion inflamed cremaster muscle venules. Furthermore, identified as critical component for extravasation peritoneal cavity. Finally, also revealed phagocytosis Escherichia coli particles absence KV1.3. Conclusion We signalling processes. Our findings do not only provide evidence role key functions these cells, they open up new therapeutic approaches treat disorders characterized overwhelming infiltration.

Language: Английский

Citations

38
Src family kinases (SFKs): critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson's and Alzheimer's diseases DOI Open Access
Camila C. Portugal, Tiago O. Almeida, Renato Socodato

et al.

FEBS Journal, Journal Year: 2021, Volume and Issue: 289(24), P. 7760 - 7775

Published: Sept. 12, 2021

c-Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification other tyrosine-phosphorylating kinases with a similar structure gave rise concept Src family (SFKs). Microglia are resident innate immune cell population CNS. Under physiological conditions, microglia actively participate in brain tissue homeostasis, continuously patrolling neuronal parenchyma and exerting neuroprotective actions. Activation pathogen-associated molecular pattern (PAMP) damage-associated (DAMP) receptors induces microglial proliferation, migration toward pathological foci, phagocytosis, changes gene expression, concurrent secretion cytokines, chemokines, growth factors. A significant body literature shows that SFK stimulation positively associates activation neuropathological including Alzheimer's Parkinson's diseases. Here, we review essential homeostatic functions regulated by SFKs, environmental sensing, inflammatory mediators. In addition, discuss potential modulation for homeostasis

Language: Английский

Citations

37
Unique molecular characteristics and microglial origin of Kv1.3 channel–positive brain myeloid cells in Alzheimer’s disease DOI

Supriya Ramesha,

Sruti Rayaprolu, Christine A Bowen

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(11)

Published: March 1, 2021

Significance The potassium channel Kv1.3 in brain myeloid cells represents a promising therapeutic target for Alzheimer’s disease (AD). patterns of expression and functional roles channels subpopulations the microglial-versus-peripheral origin Kv1.3-expressing AD remain unclear. Here, we show that mice, is selectively up-regulated an Aβ-dependent manner by subset microglia-derived cells, expresses higher levels proinflammatory genes, confirms presence microglial human AD. Furthermore, blocking model reduces Aβ neuropathology, increases synaptic protein expression, skews transcriptome toward pro-phagocytic protective phenotypes. Our findings strengthen preclinical rationale targeting immunomodulation

Language: Английский

Citations

36
Fyn Kinase Activity and Its Role in Neurodegenerative Disease Pathology: a Potential Universal Target? DOI
Bianca Guglietti,

Srisankavi Sivasankar,

Sanam Mustafa

et al.

Molecular Neurobiology, Journal Year: 2021, Volume and Issue: 58(11), P. 5986 - 6005

Published: Aug. 25, 2021

Language: Английский

Citations

33
The Mechanism and Function of Glia in Parkinson's Disease DOI Creative Commons
Xinguo Zhang, Ruiqi Zhang, Maher Un Nisa Awan

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: May 26, 2022

Parkinson's disease (PD) is a neurodegenerative that primarily affects elderly people. The mechanism on onset and progression of PD unknown. Currently, there are no effective treatment strategies for PD. thought to be the loss midbrain dopaminergic neurons, but it has recently been discovered glia also brain tissue homeostasis, defense, repair in process linked both losses glial supportive-defensive functions toxic gain functions. In this article, we reviewed roles microglia, astrocytes, oligodendrocytes development PD, as well potential use glia-related medications treatment.

Language: Английский

Citations

23
The roles of fungus in CNS autoimmune and neurodegeneration disorders DOI Creative Commons

Chuyu Wu,

Meiling Jiang,

Runqui Jiang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 26, 2023

Fungal infection or proliferation in our body is capable of initiation strong inflammation and immune responses that result different consequences, including infection-trigged organ injury inflammation-related remote dysfunction. Fungi associated infectious diseases have been well recognized the clinic. However, whether fungi play an important role non-infectious central nervous system disease still to be elucidated. Recently, a growing amount evidence point non-negligible peripheral fungus triggering unique inflammation, response, exacerbation range CNS disorders, Multiple sclerosis, Neuromyelitis optica, Parkinson’s disease, Alzheimer’s Amyotrophic lateral sclerosis et al. In this review, we summarized recent advances recognizing patterns inflammatory signaling subsets cells, with specific focus on its function autoimmune neurodegeneration diseases. conclusion, by multiple mechanisms progression diseases, suggesting it serves as key factor critical novel target for development potential therapeutic strategies.

Language: Английский

Citations

16