Novel Activity of Oral Hypoglycemic Agents Linked with Decreased Formation of Tryptophan Metabolite, Kynurenic Acid DOI Creative Commons
Kinga Bednarz,

Kamila Kozieł,

Ewa M. Urbańska

et al.

Life, Journal Year: 2024, Volume and Issue: 14(1), P. 127 - 127

Published: Jan. 15, 2024

Kynurenic acid is a tryptophan (Trp) metabolite formed along the kynurenine (KYN) pathway in brain and peripheral tissues. The disturbed formation of kynurenic acid, which targets glutamate-mediated neurotransmission, GPR35, aryl hydrocarbon receptors immune or redox status, was implicated development neuropsychiatric metabolic disorders among others. exerts neuroprotective immunomodulatory effects, yet its high levels may negatively impact cognition. Changes Trp–KYN are also linked with pathogenesis diabetes mellitus, an established risk factor for cardiovascular neurological diseases cognitive deficits. Here, effects metformin glibenclamide on synthesis were evaluated. Acute exposure rat cortical slices vitro to either drugs reduced production de novo. Glibenclamide, but not metformin, inhibited activity biosynthetic enzymes, aminotransferases (KATs) I II, semi-purified homogenates. availability be regarded as unwanted effect, possibly alleviating action oral hypoglycemic agents. On other hand, considering that both compounds ameliorate deficits animal human studies hamper learning memory, diminished improve

Language: Английский

Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential DOI Open Access
Roman Roy, Joshua Wilcox, David J. Webb

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15200 - 15200

Published: Oct. 15, 2023

Nitric oxide (NO) plays an important and diverse signalling role in the cardiovascular system, contributing to regulation of vascular tone, endothelial function, myocardial haemostasis, thrombosis, amongst many other roles. NO is synthesised through nitric synthase (NOS)-dependent L-arginine-NO pathway, as well nitrate-nitrite-NO pathway. The three isoforms NOS, namely neuronal (NOS1), inducible (NOS2), (NOS3), have different localisation functions human body, are consequently thought differing pathophysiological Furthermore, we continue develop a deepened understanding roles NOS disease, possibility therapeutically modulating activity has emerged. Indeed, impaired (or dysfunctional), overactive dysregulated) attractive therapeutic targets disease. This review aims describe recent advances elucidating physiological within mechanisms dysfunctional dysregulated We then discuss modulation target development novel therapeutics.

Language: Английский

Citations

47
Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones DOI Creative Commons
Maryam Adenike Salaudeen, Nura Bello,

Rabi’u Nuhu Danraka

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 305 - 305

Published: March 4, 2024

The majority of approved therapies for many diseases are developed to target their underlying pathophysiology. Understanding disease pathophysiology has thus proven vital the successful development clinically useful medications. Stroke is generally accepted as leading cause adult disability globally and ischemic stroke accounts most common form two main types. Despite its health socioeconomic burden, there still minimal availability effective pharmacological treatment. In this review, we take an in-depth look at etiology stroke, including molecular cellular changes. This followed by a highlight drugs, therapies, complementary medicines that or undergoing clinical trials treatment management stroke. We also identify unexplored potential targets in pathogenesis can be exploited increase pool anti-stroke neuroprotective agents through de novo drug repurposing.

Language: Английский

Citations

31
Neuroprotective mechanisms of luteolin in glutamate-induced oxidative stress and autophagy-mediated neuronal cell death DOI Creative Commons
Wudtipong Vongthip, Sunita Nilkhet,

Kanokkan Boonruang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 2, 2024

Abstract Neurodegenerative diseases, characterized by progressive neuronal dysfunction and loss, pose significant health challenges. Glutamate accumulation contributes to cell death in diseases such as Alzheimer's disease. This study investigates the neuroprotective potential of Albizia lebbeck leaf extract its major constituent, luteolin, against glutamate-induced hippocampal death. Glutamate-treated HT-22 cells exhibited reduced viability, altered morphology, increased ROS, apoptosis, which were attenuated pre-treatment with A. luteolin. Luteolin also restored mitochondrial function, decreased superoxide, preserved morphology. Notably, we first found that luteolin inhibited excessive process mitophagy via inactivation BNIP3L/NIX lysosomal activity. Our suggests autophagy-mediated is activation mTORC1. These findings highlight a agent, inhibiting neurotoxicity regulating autophagy dynamics.

Language: Английский

Citations

19
NMDA Receptor Antagonists: Emerging Insights into Molecular Mechanisms and Clinical Applications in Neurological Disorders DOI Creative Commons
Ayodeji O. Egunlusi, Jacques Joubert

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 639 - 639

Published: May 15, 2024

Neurodegenerative disorders (NDs) include a range of chronic conditions characterized by progressive neuronal loss, leading to cognitive, motor, and behavioral impairments. Common examples Alzheimer's disease (AD) Parkinson's (PD). The global prevalence NDs is on the rise, imposing significant economic social burdens. Despite extensive research, mechanisms underlying remain incompletely understood, hampering development effective treatments. Excitotoxicity, particularly glutamate-mediated excitotoxicity, key pathological process implicated in NDs. Targeting N-methyl-D-aspartate (NMDA) receptor, which plays central role holds therapeutic promise. However, challenges, such as blood-brain barrier penetration adverse effects, extrapyramidal have hindered success many NMDA receptor antagonists clinical trials. This review explores molecular antagonists, emphasizing their structure, function, types, future prospects treating research competitive noncompetitive quest for treatments still faces hurdles. partly because same that necessitates blockage under also responsible normal physiological function receptors. Allosteric modulation receptors presents potential alternative, with GluN2B subunit emerging attractive target due its enrichment presynaptic extrasynaptic receptors, are major contributors excitotoxic-induced cell death. low side-effect profiles, selective like ifenprodil radiprodil encountered obstacles poor bioavailability Moreover, selectivity these often relative, they been shown bind other GluN2 subunits, albeit minimally. Recent advancements developing phenanthroic naphthoic acid derivatives offer promise enhanced GluN2B, GluN2A or GluN2C/GluN2D improved pharmacodynamic properties. Additional challenges antagonist conflicting preclinical results, well complexity neurodegenerative poorly defined subtypes. Although multifunctional agents targeting multiple degenerative processes being explored, data limited. Designing antagonists/modulators polycyclic moieties multitarget properties would be addressing disorders. understanding structure coupled collaborative efforts drug design, imperative realizing antagonists/modulators.

Language: Английский

Citations

19
Exploring the intricacies of calcium dysregulation in ischemic stroke: Insights into neuronal cell death and therapeutic strategies DOI

Vikrant Rahi,

Ravinder K. Kaundal

Life Sciences, Journal Year: 2024, Volume and Issue: 347, P. 122651 - 122651

Published: April 19, 2024

Language: Английский

Citations

17
Stroke: Molecular mechanisms and therapies: Update on recent developments DOI Creative Commons
Faheem Shehjar,

Briana Maktabi,

Zainab A. Rahman

et al.

Neurochemistry International, Journal Year: 2022, Volume and Issue: 162, P. 105458 - 105458

Published: Nov. 30, 2022

Language: Английский

Citations

63
Repetitive transcranial magnetic stimulation for stroke rehabilitation: insights into the molecular and cellular mechanisms of neuroinflammation DOI Creative Commons

Rongjun Sheng,

Changchun Chen, Huan Chen

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 22, 2023

Stroke is a leading cause of mortality and disability worldwide, with most survivors reporting dysfunctions motor, sensation, deglutition, cognition, emotion, speech, etc. Repetitive transcranial magnetic stimulation (rTMS), one noninvasive brain (NIBS) techniques, able to modulate neural excitability regions has been utilized in neurological psychiatric diseases. Moreover, large number studies have shown that the rTMS presents positive effects on function recovery stroke patients. In this review, we would like summarized clinical benefits for rehabilitation, including improvements motor impairment, dysphagia, depression, cognitive function, central post-stroke pain. addition, review will also discuss molecular cellular mechanisms underlying rTMS-mediated especially immune regulatory mechanisms, such as regulation cells inflammatory cytokines. neuroimaging technique an important tool rehabilitation discussed, better understanding rTMS. Finally, current challenges future prospects are elucidated intention accelerate its widespread application.

Language: Английский

Citations

40
An Ultrasmall Cu/Cu2O Nanoparticle-Based Diselenide-Bridged Nanoplatform Mediating Reactive Oxygen Species Scavenging and Neuronal Membrane Enhancement for Targeted Therapy of Ischemic Stroke DOI
Jianglong Kong, Rui Zou, Runxuan Chu

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 18(5), P. 4140 - 4158

Published: Dec. 22, 2023

Ischemic stroke is one of the major causes death and disability worldwide, an effective timely treatment ischemic has been a challenge because narrow therapeutic window poor affinity with thrombus thrombolytic agent. In this study, rPZDCu, multifunctional nanoparticle (NP) effects thrombolysis, reactive oxygen species (ROS) scavenging, neuroprotection, was synthesized based on ultrasmall Cu

Language: Английский

Citations

30
Driving factors of neuronal ferroptosis DOI
Julie Jacquemyn, Isha Ralhan, Maria S. Ioannou

et al.

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(7), P. 535 - 546

Published: Feb. 23, 2024

Language: Английский

Citations

15
Molecular Pathogenesis of Ischemic and Hemorrhagic Strokes: Background and Therapeutic Approaches DOI Open Access
Carlo Maida, Rosario Luca Norrito,

Salvatore Rizzica

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6297 - 6297

Published: June 7, 2024

Stroke represents one of the neurological diseases most responsible for death and permanent disability in world. Different factors, such as thrombus, emboli atherosclerosis, take part intricate pathophysiology stroke. Comprehending molecular processes involved this mechanism is crucial to developing new, specific efficient treatments. Some common mechanisms are excitotoxicity calcium overload, oxidative stress neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) critical recovery after cerebral ischemia. ncRNAs, particularly microRNAs, long (lncRNAs) essential angiogenesis neuroprotection, they have been suggested be therapeutic, diagnostic prognostic tools cerebrovascular diseases, including This review summarizes underlying ischemic hemorrhagic stroke delves into function miRNAs development brain damage. we will analyze new perspectives on treatment based addition traditional therapies.

Language: Английский

Citations

13