Role of the Angiotensin Pathway and its Target Therapy in Epilepsy Management DOI Open Access
Shaip Krasniqi, Armond Daci

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(3), P. 726 - 726

Published: Feb. 8, 2019

Despite extensive research on epileptogenesis, there is still a need to investigate new pathways and targeted therapeutic approaches in this complex process. Inflammation, oxidative stress, neurotoxicity, neural cell death, gliosis, blood–brain barrier (BBB) dysfunction are the most common causes of epileptogenesis. Moreover, renin–angiotensin system (RAS) affects brain’s physiological pathological conditions, including epilepsy its consequences. While variety available pharmacotherapeutic approaches, information high demand achievement treatment goals greatly desired. Therefore, targeting RAS presents an interesting opportunity better understand This has been supported by preclinical studies, primarily based enzyme, receptor-inhibition, selective agonists, which characterized pleiotropic properties. Although some antiepileptic drugs (AEDs) that interfere with RAS, main therapy pathway contributes synergy AEDs. However, RAS-targeted alone, or combination AEDs, requires clinical studies contribute to, clarify, evidence management. There also genetic association between epilepsy, involvement pharmacogenetics so possibilities for development diagnostic personalized treatments epilepsy.

Language: Английский

Drugs repurposing in the experimental models of Alzheimer’s disease DOI Creative Commons

Sheer A. Joodi,

Weam W. Ibrahim, Mahmoud M. Khattab

et al.

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract The currently approved drugs for Alzheimer’s disease (AD) are only symptomatic treatment in the early stages of but they could not halt neurodegeneration, additionally, safety profile recently developed immunotherapy is a big issue. This review aims to explain importance repurposing technique and strategy develop therapy AD. We illustrated biological alterations pathophysiology AD including amyloid pathology, Tau oxidative stress, mitochondrial dysfunction, neuroinflammation, glutamate-mediated excitotoxicity, insulin signaling impairment, wingless-related integration site/ β -catenin signaling, autophagy. Additionally, we demonstrated different repurposed experimental models anti-inflammatory, anti-hypertensive, anti-diabetic, antiepileptic, antidepressant anticancer drugs. Further, showed pipeline FDA have promising therapeutic activity against AD, confirming value elucidate curative Graphical abstract

Language: Английский

Citations

1
Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury DOI Open Access
Murat Öz, Dietrich E. Lorke

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 136, P. 111193 - 111193

Published: Jan. 8, 2021

The recent emergence of coronavirus disease-2019 (COVID-19) as a pandemic affecting millions individuals has raised great concern throughout the world, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was identified causative agent for COVID-19. multifunctional protein angiotensin converting enzyme 2 (ACE2) is accepted its primary target entry into host cells. In enzymatic function, ACE2, like homologue ACE, regulates renin-angiotensin system (RAS) critical cardiovascular renal homeostasis in mammals. Unlike however, ACE2 drives an alternative RAS pathway by degrading Ang-II thus operates to balance context hypertension, heart failure, well complications diabetes. Outside RAS, hydrolyzes key peptides, such amyloid-β, apelin, [des-Arg9]-bradykinin. addition functions, found regulate intestinal amino acid gut microbiome. Although non-enzymatic function receptor SARS-CoV-2 been established, contribution functions pathogenesis COVID-19-related lung injury matter debate. A complete understanding this central may begin explain various symptoms pathologies seen infected individuals, aid development novel treatments

Language: Английский

Citations

53
Activation of angiotensin‐converting enzyme 2/angiotensin (1–7)/mas receptor axis triggers autophagy and suppresses microglia proinflammatory polarization via forkhead box class O1 signaling DOI Creative Commons
Ruili Dang, Mengqi Yang, Changmeng Cui

et al.

Aging Cell, Journal Year: 2021, Volume and Issue: 20(10)

Published: Sept. 16, 2021

Brain renin-angiotensin (Ang) system (RAS) is implicated in neuroinflammation, a major characteristic of aging process. Angiotensin II, produced by angiotensin-converting enzyme (ACE), activates immune via angiotensin type 1 receptor (AT1), whereas Ang(1-7), generated ACE2, binds with Mas (MasR) to restrain excessive inflammatory response. Therefore, the present study aims explore relationship between RAS and neuroinflammation. We found that repeated lipopolysaccharide (LPS) treatment shifted balance ACE/Ang II/AT1 ACE2/Ang(1-7)/MasR axis deleterious side either MasR agonist, AVE0991 (AVE) or ACE2 activator, diminazene aceturate, exhibited strong neuroprotective actions. Mechanically, activation triggered Forkhead box class O1 (FOXO1)-autophagy pathway induced superoxide dismutase (SOD) catalase (CAT), FOXO1-targeted antioxidant enzymes. Meanwhile, knockdown FOXO1 BV2 cells, using selective inhibitor, AS1842856, animals, suppressed translocation compromised autophagic process activation. further used chloroquine (CQ) block autophagy showed suppressing abrogated anti-inflammatory action AVE. Likewise, Ang(1-7) also signaling flux following LPS cells. Cotreatment AS1842856 CQ all led inhibition thereby abolished Ang(1-7)-induced remission on NLRP3 inflammasome caused exposure, shifting microglial polarization from M1 M2 phenotype. Collectively, these results firstly illustrated mechanism strongly indicating involvement FOXO1-mediated neuroimmune-modulating effects

Language: Английский

Citations

45
Intranasal Oxytocin Attenuates Cognitive Impairment, β-Amyloid Burden and Tau Deposition in Female Rats with Alzheimer’s Disease: Interplay of ERK1/2/GSK3β/Caspase-3 DOI Creative Commons
Samar O. El-Ganainy, Omar Soliman,

Aya A. Ghazy

et al.

Neurochemical Research, Journal Year: 2022, Volume and Issue: 47(8), P. 2345 - 2356

Published: May 20, 2022

Oxytocin is a neuropeptide hormone that plays an important role in social bonding and behavior. Recent studies indicate oxytocin could be involved the regulation of neurological disorders. However, its modulating cognition Alzheimer's disease (AD) has never been explored. Hence, present study aims to investigate potential chronic intranasal halting memory impairment & AD pathology aluminum chloride-induced female rats. Morris water maze was used assess cognitive dysfunction two-time points throughout treatment period. In addition, neuroprotective effects were examined by assessing hippocampal acetylcholinesterase activity, β-amyloid 1-42 protein, Tau levels. ERK1/2, GSK3β, caspase-3 levels assessed as chief neurobiochemical mediators AD. Hippocampi histopathological changes also evaluated. These findings compared standard drug galantamine alone combined with oxytocin. Results showed restored functions improved animals' behavior test. This accompanied significant decline proteins Hippocampal ERK1/2 GSK3β reduced, exceeding effects, thus attenuating pathological hallmarks formation. Determination revealed low cytoplasmic positivity, indicating ceasing neuronal death. Histopathological examination confirmed these findings, showing cells structure. Combined even better biochemical profiles. It can concluded possesses promising mediated via restoring suppressing β-amyloid, accumulation,

Language: Английский

Citations

31
NLRP3 inflammasome inhibition and M1-to-M2 microglial polarization shifting via scoparone-inhibited TLR4 axis in ovariectomy/D-galactose Alzheimer's disease rat model DOI
Weam W. Ibrahim, Krystyna Skalicka‐Woźniak, Barbara Budzyńska

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 119, P. 110239 - 110239

Published: May 1, 2023

Language: Английский

Citations

23
Role of brain renin–angiotensin system in depression: A new perspective DOI Creative Commons

Naif H. Ali,

Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 30(4)

Published: Nov. 12, 2023

Abstract Depression is a mood disorder characterized by abnormal thoughts. The pathophysiology of depression related to the deficiency serotonin (5HT), which derived from tryptophan (Trp). Mitochondrial dysfunction, oxidative stress, and neuroinflammation are involved in pathogenesis depression. Notably, renin–angiotensin system (RAS) depression, different findings revealed that angiotensin‐converting enzyme inhibitors (ACEIs) angiotensin receptor blockers (ARBs) may be effective However, underlying mechanism for role dysregulated brain RAS‐induced remains speculative. Therefore, this review aimed revise conceivable ACEIs ARBs how these agents ameliorate Dysregulation RAS triggers development progression through reduction 5HT expression brain‐derived neurotrophic factor (BDNF) induction mitochondrial neuroinflammation. inhibition central classical ARBS activation non‐classical prevent regulating 5HT, BDNF,

Language: Английский

Citations

19
The potential role of brain renin‐angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat? DOI Creative Commons
Zainah Al‐Qahtani, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(12)

Published: June 1, 2024

Abstract Parkinson disease (PD) is one of the most common neurodegenerative diseases brain. Of note, brain renin‐angiotensin system (RAS) intricate in PD neuropathology through modulation oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, RAS by angiotensin receptor blockers (ARBs) angiotensin‐converting enzyme inhibitors (ACEIs) may be effective reducing risk neuropathology. It has been shown that all components including peptides enzymes are present different areas. Brain plays a critical role regulation memory cognitive function, controlling central blood pressure. However, exaggerated implicated pathogenesis PD. Two well‐known pathways recognized including; classical pathway which mainly mediated AngII/AT1R detrimental effects. Conversely, non‐classical mostly ACE2/Ang1‐7/MASR AngII/AT2R beneficial effects against Exaggerated affects viability dopaminergic neurons. fundamental mechanism was not fully elucidated. Consequently, purpose this review to disclose mechanistic In addition, we try revise how ACEIs ARBs can developed for therapeutics

Language: Английский

Citations

7
Effect of Resveratrol on Reactive Oxygen Species-Induced Cognitive Impairment in Rats with Angiotensin II-Induced Early Alzheimer’s Disease † DOI Open Access
Yu‐Te Lin,

Yi‐Chung Wu,

Gwo‐Ching Sun

et al.

Journal of Clinical Medicine, Journal Year: 2018, Volume and Issue: 7(10), P. 329 - 329

Published: Oct. 5, 2018

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer's disease (AD). However, relationships among AD, hypertension, oxidative stress remain to be elucidated. Here, we aimed determine whether reactive oxygen species (ROS) reduction by resveratrol in brain leads cognitive impairment rats with angiotensin II (Ang-II)-induced early AD. Male Wistar Kyoto (WKY) Ang-II-induced AD were treated losartan or for two weeks. Our results show decreased blood pressure, increased hippocampal brain-derived neurotrophic factor (BDNF) level, nucleus tractus solitarius (NTS) ROS production Ang-II groups (10 mg/kg), mg/kg/day) treatment. Furthermore, inhibition TauT231 phosphorylation activated AktS473 phosphorylation, significantly abolished Aβ precursors, active caspase 3, glycogen synthase kinase 3β (GSK-3β)Y216 expressions. Consistently, showed similar effects compared losartan. Both restored hippocampal-dependent contextual memory NADPH oxidase 2 (NOX2) deletion superoxide dismutase (SOD2) elevation. suggest both exert neuroprotective against damage stage rat model. These novel findings indicate represent a pharmacological option patients hypertension at risk during old age.

Language: Английский

Citations

56
Effect of spinal angiotensin-converting enzyme 2 activation on the formalin-induced nociceptive response in mice DOI
Wataru Nemoto,

Ryota Yamagata,

Osamu Nakagawasai

et al.

European Journal of Pharmacology, Journal Year: 2020, Volume and Issue: 872, P. 172950 - 172950

Published: Jan. 25, 2020

Language: Английский

Citations

49
Dimethyl fumarate abridged tauo-/amyloidopathy in a D-Galactose/ovariectomy-induced Alzheimer's-like disease: Modulation of AMPK/SIRT-1, AKT/CREB/BDNF, AKT/GSK-3β, adiponectin/Adipo1R, and NF-κB/IL-1β/ROS trajectories DOI

Israa M Abd El-Fatah,

Heba M. A. Abdelrazek, Sherehan M. Ibrahim

et al.

Neurochemistry International, Journal Year: 2021, Volume and Issue: 148, P. 105082 - 105082

Published: May 28, 2021

Language: Английский

Citations

37