Clinical Trials of New Drugs for Vascular Cognitive Impairment and Vascular Dementia

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(19), С. 11067 - 11067

Опубликована: Сен. 21, 2022

Population aging has challenged the treatment of cognitive impairment or dementia. Vascular dementia is second leading cause after Alzheimer's disease. Cognitive consequences ischemic brain injury have been recognized as a preferred target for therapeutic strategies, prompting search potential agents. The keyword "vascular dementia" was used to ClinicalTrials.gov determine agents represented in phases I, II, III, and IV. were classified on basis their mechanisms. Of 17 randomized controlled trials meeting our inclusion criteria, 9 completed past 10 years, 8 are ongoing planning stages. We also identified one trial phase nine six Fewer new drugs improving cognition ameliorating behavioral psychological symptoms vascular than Drug overlap with drug targeting functional outcomes cerebrovascular International pharmaceutical companies' investment VCI remains insufficient.

Язык: Английский

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Nitric oxide is not just blowing in the wind

British Journal of Pharmacology, Год журнала: 2018, Номер 176(2), С. 131 - 134

Опубликована: Дек. 16, 2018

Linked Articles This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view other articles in this visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc

Язык: Английский

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Coordination between Calcium/Calmodulin-Dependent Protein Kinase II and Neuronal Nitric Oxide Synthase in Neurons

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(21), С. 7997 - 7997

Опубликована: Окт. 27, 2020

Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is highly abundant in the brain and exhibits broad substrate specificity, thereby it thought to participate regulation of neuronal death survival. Nitric oxide (NO), produced by NO synthase (nNOS), an important neurotransmitter plays a role activity including learning memory processes. However, high levels can contribute excitotoxicity following stroke neurodegenerative disease. Aside from NO, nNOS also generates superoxide which involved both cell injury signaling. CaMKII known activate translocate cytoplasm post-synaptic density response activation where predominantly located. Phosphorylation at Ser847 decreases generation increases generation. Conversely, NO-induced S-nitrosylation Cys6 prominent determinant inhibition ATP competitive fashion. Thus, “cross-talk” between NO/superoxide may represent signal transduction pathways brain. In this review, we introduce molecular mechanism pathophysiological mutual neurons.

Язык: Английский

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Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging

Antioxidants, Год журнала: 2023, Номер 12(10), С. 1844 - 1844

Опубликована: Окт. 10, 2023

The aim of this review is to explore the relationship between melatonin, free radicals, and non-excitatory amino acids, their role in stroke aging. Melatonin has garnered significant attention recent years due its diverse physiological functions potential therapeutic benefits by reducing oxidative stress, inflammation, apoptosis. been found mitigate ischemic brain damage caused stroke. By scavenging radicals damage, melatonin may help slow down aging process protect against age-related cognitive decline. Additionally, acids have shown possess neuroprotective properties, including antioxidant anti-inflammatory aging-related conditions. They can attenuate modulate calcium homeostasis, inhibit apoptosis, thereby safeguarding neurons induced processes. intracellular accumulation certain could promote harmful effects during hypoxia-ischemia episodes thus, blockade acid transporters involved be an alternative strategy reduce damage. On other hand, specifically mitochondrial reactive oxygen nitrogen species, accelerates cellular senescence contributes Recent research suggests a complex interplay actions converge on multiple pathways, regulation modulation reduction inflammation. These mechanisms collectively contribute preservation neuronal integrity functions, making them promising targets for interventions disorders.

Язык: Английский

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The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 9071 - 9071

Опубликована: Авг. 21, 2024

Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then exert tight control over much broader range of processes, including neurotransmitter release, neuronal excitability, synaptic plasticity. Endothelial NO synthase (eNOS) usually far from the mind neurophysiologists, who have focused most their attention on (nNOS) as primary source at neurovascular unit (NVU). Nevertheless, available evidence suggests eNOS could also contribute generating burst that, serving volume intercellular messenger, produced in response activity brain parenchyma. Herein, we review role both regulation cerebral blood flow plasticity discuss mechanisms by which cerebrovascular endothelial cells may transduce inputs into signal. We further suggest play critical vascular-to-neuronal communication integrating signals converging onto streaming active neurons.

Язык: Английский

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Erectile Function and Sexual Behavior: A Review of the Role of Nitric Oxide in the Central Nervous System

Biomolecules, Год журнала: 2021, Номер 11(12), С. 1866 - 1866

Опубликована: Дек. 11, 2021

Nitric oxide (NO), the neuromodulator/neurotransmitter formed from l-arginine by neuronal, endothelial and inducible NO synthases, is involved in numerous functions across body, control of arterial blood pressure to penile erection, at central level energy homeostasis regulation memory, learning sexual behavior. The aim this work review earlier studies showing that plays a role erectile function behavior hypothalamus its paraventricular nucleus medial preoptic area, integrate these findings with those recent on matter. This revisitation shows influences males females acting not only area but also extrahypothalamic brain areas, often different mechanisms. Most importantly, since areas are strictly interconnected send receive neural projections spinal cord, which communication between genital apparatus takes place, reveals participates concert neurotransmitters/neuropeptides circuit controlling both consummatory (penile copulation, lordosis) appetitive components (sexual motivation, arousal, reward)

Язык: Английский

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Nitric Oxide Signal Transduction and Its Role in Skin Sensitization

Biomolecules & Therapeutics, Год журнала: 2023, Номер 31(4), С. 388 - 394

Опубликована: Июнь 22, 2023

Nitric oxide (NO) is a signaling molecule that plays crucial role in numerous cellular physiological processes.In the skin, NO produced by keratinocytes, fibroblasts, endothelial cells, and immune cells involved skin functions such as vasodilation, pigmentation, hair growth, wound healing, responses.NO modulates both innate adaptive responses.As cytotoxic effector, influences function of production cytokines.NO key mediator protects against or contributes to inflammation.Moreover, has been implicated sensitization, process underlying contact dermatitis.It dendritic T thereby affecting response allergens.NO also dermatitis inducing inflammation tissue damage.NO-related chemicals, nitrofatty acids nitric synthase (NOS) inhibitors, have potential therapeutic applications conditions, including allergic (ACD) irritant (ICD).Further research required fully elucidate NO-related chemicals develop personalized treatment strategies for conditions.

Язык: Английский

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Wheel‐Running Exercise Alleviates Anxiety‐Like Behavior via Down‐Regulating S‐Nitrosylation of Gephyrin in the Basolateral Amygdala of Male Rats

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 4, 2024

Physical exercise has beneficial effect on anxiety disorders, but the underlying molecular mechanism remains largely unknown. Here, it is demonstrated that physical can downregulate S-nitrosylation of gephyrin (SNO-gephyrin) in basolateral amygdala (BLA) to exert anxiolytic effects. It found level SNO-gephyrin significantly increased BLA high-anxiety rats and a downregulation at cysteines 212 284 produced effect. Mechanistically, inhibition by either Cys212 or Cys284 mutations surface expression GABA

Язык: Английский

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Ex Tenebris Lux: Illuminating Reactive Oxygen and Nitrogen Species with Small Molecule Probes

Chemical Reviews, Год журнала: 2024, Номер 124(16), С. 9225 - 9375

Опубликована: Авг. 13, 2024

Reactive oxygen and nitrogen species are small reactive molecules derived from elements in the air─oxygen nitrogen. They produced biological systems to mediate fundamental aspects of cellular signaling but must be very tightly balanced prevent indiscriminate damage molecules. Small molecule probes can transmute specific nature each into an observable luminescent signal (or even acoustic wave) offer sensitive selective imaging living cells whole animals. This review focuses specifically on for superoxide, hydrogen peroxide, hypochlorite, nitric oxide, peroxynitrite that provide a or photoacoustic signal. Important background information general photophysical phenomena, common probe designs, mechanisms, modalities will provided, then, analyte thoroughly evaluated. A discussion successes field presented, followed by recommendations improvement future outlook emerging trends. Our objectives informative, useful, thorough guide as well important context compare ecosystem chemistries molecular scaffolds has manifested within field.

Язык: Английский

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Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders

Cells, Год журнала: 2025, Номер 14(2), С. 86 - 86

Опубликована: Янв. 9, 2025

Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among 11 PDE subtypes, PDE4 PDE5 are particularly significant due to their regulation cyclic adenosine monophosphate (cAMP) guanosine (cGMP) signaling, respectively, which vital learning, memory, neuroprotection. This review synthesizes current evidence on roles in health disease, focusing second messenger implications function. Elevated activity impairs synaptic plasticity by reducing cAMP levels protein kinase A (PKA) activity, contributing cognitive decline, acute injuries, neuropsychiatric conditions such as bipolar disorder schizophrenia. Similarly, dysregulation disrupts nitric oxide (NO) G (PKG) pathways, involved cerebrovascular homeostasis, recovery after ischemic events, neurodegenerative processes Alzheimer's, Parkinson's, Huntington's diseases. promising therapeutic targets Pharmacological modulation these offers potential enhance function mitigate pathological mechanisms underlying diseases, psychiatric Further research into will advance strategies conditions.

Язык: Английский

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