Biological hypotheses, risk factors, and biomarkers of schizophrenia

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2022, Volume and Issue: 120, P. 110626 - 110626

Published: Aug. 31, 2022

Language: Английский

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Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

Antioxidants, Journal Year: 2022, Volume and Issue: 11(10), P. 2049 - 2049

Published: Oct. 18, 2022

In the last few decades, endocannabinoids, plant-derived cannabinoids and synthetic have received growing interest as treatment options in neurodegenerative conditions. various experimental settings, they displayed antioxidative, anti-inflammatory, antiapoptotic, immunomodulatory, neuroprotective effects. However, due to numerous targets downstream effectors of their action, cellular molecular mechanisms underlying these effects are rather complex still under discussion. Cannabinoids able neutralize free radicals modulate production reactive oxygen species activity antioxidative systems acting on CB1 CB2 cannabinoid receptors. The activation receptors stimulates signaling pathways involved defense survival (such phosphoinositide 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), Nrf2 pathways) regulates glutamatergic signaling, N-methyl-D-aspartate (NMDA) receptors, calcium influx, induction Ca2+-regulated cascades, whereas mediated by suppression microglial release prooxidative proinflammatory mediators. This review summarizes main new advances understanding cannabinoids. Because plethora possible pharmacological interventions related oxidative stress cannabinoid-mediated neuroprotection, future research should be directed towards a better interplay between activated signal transduction with aim improve efficacy targeting endocannabinoid system.

Language: Английский

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Endocannabinoid System: Chemical Characteristics and Biological Activity

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 148 - 148

Published: Jan. 19, 2023

The endocannabinoid system (eCB) has been studied to identify the molecular structures present in Cannabis sativa. eCB consists of cannabinoid receptors, endogenous ligands, and associated enzymatic apparatus responsible for maintaining energy homeostasis cognitive processes. Several physiological effects cannabinoids are exerted through interactions with various such as CB1 CB2 vanilloid recently discovered G-protein-coupled receptors (GPR55, GPR3, GPR6, GPR12, GPR19). Anandamide (AEA) 2-arachidoylglycerol (2-AG), two small lipids derived from arachidonic acid, showed high-affinity binding both receptors. plays a critical role chronic pain mood disorders extensively because its wide therapeutic potential it is promising target development new drugs. Phytocannabinoids synthetic have shown varied affinities relevant treatment several neurological diseases. This review provides description components discusses how phytocannabinoids other exogenous compounds may regulate balance. Furthermore, we show hypo- or hyperfunctionality body related disorders, even integrative complementary health practices (ICHP) harmonizing eCB.

Language: Английский

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Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 4050 - 4050

Published: April 5, 2024

Alzheimer's disease (AD), the most common neurodegenerative (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered hallmarks AD pathology. Different therapeutic approaches approved Food Drug Administration can only target a single altered pathway instead various mechanisms that involved in pathology, resulting limited symptomatic relief almost no effect slowing down progression. Growing evidence on modulating components endocannabinoid system (ECS) proclaimed their neuroprotective effects reducing neurochemical alterations preventing cellular dysfunction. Recent studies mouse models have reported inhibitors fatty acid amide hydrolase (FAAH) monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH MAGL alone or combination seem to produce neuroprotection reversing deficits along with Aβ-induced responses, death, delaying Their exact signaling need elucidated understanding brain intrinsic repair mechanism. aim this review was shed light physiology pathophysiology summarize experimental data roles inhibitors. In review, we also included CB1R CB2R modulators diverse modulate ECS mediated responses such anti-nociceptive, anxiolytic, anti-inflammatory actions AD. Future research would provide directions molecular development new interventions treatment

Language: Английский

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Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(2), P. 692 - 692

Published: Feb. 17, 2023

Previous evidence suggests that prenatal exposure to THC (pTHC) derails the neurodevelopmental trajectories towards a vulnerable phenotype for impaired emotional regulation and limbic memory. Here we aimed investigate pTHC effect on hippocampus-related cognitive functions markers of neuroplasticity in adolescent male offspring. Wistar rats were exposed (2 mg/kg) from gestational day 5 20 tested spatial memory, object recognition memory reversal learning reinforce-motivated Can test aversion-driven Barnes maze test; locomotor activity exploration, anxiety-like behaviour, response natural reward assessed open field, elevated plus maze, sucrose preference tests, respectively. The gene expression levels NMDA NR1-2A subunits, mGluR5, their respective scaffold proteins PSD95 Homer1, as well CB1R neuromodulatory protein HINT1, measured hippocampus. offspring exhibited deficits learning, increased activity, NR1-, decreased NR2A- PSD95-, mGluR5- Homer1-, augmented CB1R- HINT1-hippocampal mRNA levels. Our data shows is associated with specific impairment processing effectors hippocampal novel targets future pharmacological challenges.

Language: Английский

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Research progress on the cannabinoid type-2 receptor and Parkinson’s disease

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 8, 2024

Parkinson's disease (PD) is featured by movement impairments, including tremors, bradykinesia, muscle stiffness, and imbalance. PD also associated with many non-motor symptoms, such as cognitive dementia, mental disorders. Previous studies identify the associations between progression factors α-synuclein aggregation, mitochondrial dysfunction, inflammation, cell death. The cannabinoid type-2 receptor (CB

Language: Английский

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Assessing the role of ghrelin and the enzyme ghrelin O-acyltransferase (GOAT) system in food reward, food motivation, and binge eating behavior

Pharmacological Research, Journal Year: 2021, Volume and Issue: 172, P. 105847 - 105847

Published: Aug. 24, 2021

The peripheral peptide hormone ghrelin is a powerful stimulator of food intake, which leads to body weight gain and adiposity in both rodents humans. hormone, thus, increases the vulnerability obesity binge eating behavior. Several studies have revealed that ghrelin’s functions are due its interaction with growth secretagogue receptor type 1a (GHSR1a) hypothalamic area; besides, also promotes reinforcing properties hedonic food, acting at extra-hypothalamic sites interacting dopaminergic, cannabinoid, opioid, orexin signaling. primarily present two forms plasma enzyme O-acyltransferase (GOAT) allows acylation reaction causes transformation des-acyl-ghrelin (DAG) active form acyl-ghrelin (AG). DAG has been demonstrated show antagonist properties; it metabolically active, counteracts effects AG on glucose metabolism lipolysis, reduces consumption, weight, feeding response. Both peptides seem influence hypothalamic–pituitary–adrenal (HPA) axis corticosterone/cortisol level drive urge eat under stressful conditions. These findings suggest inhibition GOAT may be targets for bingeing-related disorders AG/DAG ratio an important potential biomarker assess risk developing maladaptive behaviors.

Language: Английский

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Differential Effects of Endocannabinoids on Amyloid-Beta Aggregation and Toxicity

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 911 - 911

Published: Jan. 4, 2023

The regulation and metabolism of the endocannabinoid system has received extensive attention for their potential neuroprotective effect in neurodegenerative diseases such as Alzheimer's disease (AD), which is characterized by amyloid β (Aβ) -induced cell toxicity, inflammation, oxidative stress. Using vitro techniques two lines, mouse hippocampus-derived HT22 cells Chinese hamster ovary (CHO) expressing human cannabinoid receptor type 1 (CB1), we investigated ability endocannabinoids to inhibit Aβ aggregation protect against toxicity. present study provides evidence that N-arachidonoyl ethanol amide (AEA), noladin O-arachidonoyl ethanolamine (OAE) Aβ42 aggregation. They were able provide protection induced cytotoxicity via receptor-mediated non-receptor-mediated mechanisms CB1-CHO cells, respectively. kinetic experiments demonstrate anti-Aβ activity some (AEA, noladin). These data role application AD pathology treatment.

Language: Английский

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Modulatory role of the endocannabinoidome in the pathophysiology of the gastrointestinal tract

Pharmacological Research, Journal Year: 2021, Volume and Issue: 175, P. 106025 - 106025

Published: Dec. 6, 2021

Language: Английский

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Cannabinoid CB2 Receptors in Neurodegenerative Proteinopathies: New Insights and Therapeutic Potential

Biomedicines, Journal Year: 2022, Volume and Issue: 10(12), P. 3000 - 3000

Published: Nov. 22, 2022

Some of the most prevalent neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease, are proteinopathies characterized by accumulation specific protein aggregates in brain. Such misfolded can trigger modulation innate adaptive immune systems subsequently lead to chronic neuroinflammation that drives onset progression diseases. Since there is still no effective disease-modifying treatment, new therapeutic targets for have been sought. The endocannabinoid system, particular cannabinoid CB2 receptors, extensively studied, due their important role neuroinflammation, especially microglial cells. Several studies shown promising effects receptor activation on reducing aggregation-based pathology as well attenuating inflammation several dementia-related symptoms. In this review, we discuss available data receptors potential benefits limitations agonists these therapy proteinopathies.

Language: Английский

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