Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy DOI Creative Commons
Sonia Burgaz, Elisa Navarro, Santiago Rodríguez-Carreiro

и другие.

Behavioral and Brain Functions, Год журнала: 2024, Номер 20(1)

Опубликована: Ноя. 1, 2024

The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ afforded neuroprotection in experimental models of Parkinson's disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties a PD model that also involves protein dysregulation, other key event pathogenesis.

Язык: Английский

Frontal Cortex Lipid Alterations During the Onset of Alzheimer’s Disease DOI
Marta Moreno‐Rodríguez, Sylvia E. Perez, Jonatan Martínez‐Gardeazabal

и другие.

Journal of Alzheimer s Disease, Год журнала: 2024, Номер 98(4), С. 1515 - 1532

Опубликована: Апрель 2, 2024

Background: Although sporadic Alzheimer’s disease (AD) is a neurodegenerative disorder of unknown etiology, familial AD associated with specific gene mutations. A commonality between these forms that both display multiple pathogenic events including cholinergic and lipid dysregulation. Objective: We aimed to identify the relevant lipids activity their related receptors in frontal cortex correlating them cognition during progression AD. Methods: MALDI-mass spectrometry imaging (MSI) functional autoradiography was used evaluate distribution phospholipids/sphingolipids cannabinoid 1 (CB1), sphingosine 1-phosphate (S1P1), muscarinic M2/M4 (FC) people come autopsy premortem clinical diagnosis AD, mild cognitive impairment (MCI), no (NCI). Results: MALDI-MSI revealed an increase myelin-related lipids, such as diacylglycerol (DG) 36:1, DG 38:5, phosphatidic acid (PA) 40:6 white matter (WM) MCI compared NCI, downregulation WM phosphatidylinositol (PI) 38:4 PI 38:5 levels NCI. Elevated phosphatidylcholine (PC) 32:1, PC 34:0, sphingomyelin 38:1 were observed discrete accumulations FC supragranular layers progression. Muscarinic receptor activation V-VI decreased MCI. CB1 upregulated V-VI, while S1P1 downregulated within relative Conclusions: lipidomic alterations are myelin dyshomeostasis prodromal suggesting maintenance potential therapeutic target for dementia.

Язык: Английский

Процитировано

7

Neurolipid systems: A new target for the treatment of dementia DOI Creative Commons
Gorka Pereira‐Castelo, Iker Bengoetxea de Tena, Jonatan Martínez‐Gardeazabal

и другие.

Basic & Clinical Pharmacology & Toxicology, Год журнала: 2024, Номер 135(3), С. 225 - 236

Опубликована: Июль 22, 2024

Abstract Neurolipids comprise a diverse class of bioactive lipids that include molecules capable activating G protein‐coupled receptors, thereby inducing systemic effects contribute to the maintenance homeostasis. Dementia, non‐specific brain disorder characterized by common set signs and symptoms, usually arises subsequent injuries or diseases is often associated with aging process. Individuals affected dementia suffer from disruption several neurotransmitter neuromodulatory systems, among which neurolipids play an important role, including endocannabinoid, lysophosphatidic acid sphingosine 1‐phosphate systems. In this review, we present overview most recent pertinent findings regarding involvement these neurolipidic systems in dementia, data wide range both vitro vivo experiments as well clinical trials.

Язык: Английский

Процитировано

4

Cognitive improvement via cortical cannabinoid receptors and choline‐containing lipids DOI Creative Commons
Marta Moreno‐Rodríguez, Jonatan Martínez‐Gardeazabal, Iker Bengoetxea de Tena

и другие.

British Journal of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 3, 2024

Background and Purpose Recent research linking choline‐containing lipids to degeneration of basal forebrain cholinergic neurons in neuropathological states illustrates the challenge balancing lipid integrity with optimal acetylcholine levels, essential for memory preservation. The endocannabinoid system influences learning processes regulated by neurotransmission. Therefore, we hypothesised that activation may confer neuroprotection against degeneration. Experimental Approach We examined neuroprotective potential sub‐chronic treatments cannabinoid agonist WIN55,212‐2, using ex vivo organotypic tissue cultures including nucleus basalis magnocellularis cortex rat models specific damage induced 192IgG‐saporin. Levels lipids, choline were measured histochemical immunofluorescence assays, along [ 35 S]GTPγS autoradiography muscarinic GPCRs MALDI‐mass spectrometry imaging analysis. Learning assessed Barnes maze novel object recognition test rats 3xTg‐AD mouse model. Key Results Degeneration, 192IgG‐saporin, baso‐cortical pathways resulted deficits decreased cortical levels lysophosphatidylcholines (LPC). WIN55,212‐2 restored transmission LPC via receptors. This altered homeostasis mainly reducing sphingomyelins lesioned animals. These modifications crucial recovery. Conclusion Implications hypothesise facilitates an alternative source breaking down sphingomyelins, leading elevated LPCs. results imply altering receptors presents a promising therapeutic approach dementia linked dysfunction.

Язык: Английский

Процитировано

3

Alterations in protein quality control resulting in neurodegeneration and disease DOI

Prasann Kumar

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 123 - 175

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

The emerging role of endocannabinoid system modulation in human fibroblast-like synoviocytes: Exploring new biomarkers and potential therapeutic targets DOI
Jakub Chwastek, Marta Kędziora, Małgorzata Borczyk

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 186, С. 118040 - 118040

Опубликована: Апрель 10, 2025

Язык: Английский

Процитировано

0

Exploring Membrane Cholesterol Binding to the CB1 Receptor: A Computational Perspective DOI

Manuela J. Vanegas,

Sara Gómez, Chiara Cappelli

и другие.

The Journal of Physical Chemistry B, Год журнала: 2025, Номер unknown

Опубликована: Апрель 23, 2025

Cholesterol (CHOL) is a potential allosteric modulator of the CB1 receptor. In this work, we use atomistic molecular dynamics simulations to study how CHOL interacts with and identify its binding sites (BS) residence times on specific receptor zones. Our results evince minimal changes in conformational secondary structure due CHOL. We report five BSs, three which coincide previously described interaction regions (BS1, BS2, BS3), while BS4 BS5 are proposed as new BSs. Quantum descriptors bonding such Natural Bond Orbitals (NBO), Theory Atoms Molecules (QTAIM), Noncovalent Interactions (NCI) analyses employed characterize CHOL-BS interactions. The show an exponential correlation between strength interactions (mainly hydrogen bonds hydrophobic contacts) time at Although other approaches exist high-affinity protein sites, our methodology integrates classical quantum descriptions better BSs predict ligand CB1, distinguishing persistent from transitory contacts. Since has been suggested endogenous ligand, flexible strategy allows studying that stabilize could be extended cannabinoid binding, contribute designing improved ligands.

Язык: Английский

Процитировано

0

Dysregulated Neurotransmitters and CB1 Receptor Dysfunction and Their Roles in Agitation Associated with Alzheimer’s Disease DOI Open Access
Jagadeesh S. Rao, María Alejandra Tangarife, Diego A. Rodríguez‐Soacha

и другие.

Journal of dementia and Alzheimer's disease, Год журнала: 2025, Номер 2(2), С. 15 - 15

Опубликована: Июнь 1, 2025

Alzheimer’s disease (AD) is characterized by the progressive loss of cognitive function and frequently accompanied neuropsychiatric symptoms (NPS). Pathologically, AD defined two hallmark features: extracellular accumulation β-amyloid intracellular hyperphosphorylation tau protein. In addition to these primary changes, several other abnormalities are associated with disease, including neuroinflammation, synaptic loss, oxidative stress, neurotransmitter imbalance, genetic epigenetic alterations. NPS in encompass a range symptoms, such as anxiety, apathy, agitation, depression, psychosis. These thought arise partly from damage caused pathological hallmarks AD, which impair various systems. Altered levels neurotransmitters, gamma-aminobutyric acid (GABA), serotonin (5-HT), dopamine (DA), cholinergic noradrenergic systems, have been implicated development agitation. Additionally, reduced endocannabinoid system (ECS) functionality, particularly cannabinoid receptor 1 (CB1R), has linked neurobehavioral Preclinical studies suggest that decrease CB1R aggressive behavior, agonists demonstrated beneficial effects alleviating agitation related symptoms. Given findings, current review focuses on therapeutic potential targeting systems dysfunction manage AD.

Язык: Английский

Процитировано

0

Exploring the therapeutic potential of natural compounds modulating the endocannabinoid system in various diseases and disorders: review DOI
Gidion Wilson, Lingling Yang, Xiaojuan Su

и другие.

Pharmacological Reports, Год журнала: 2023, Номер 75(6), С. 1410 - 1444

Опубликована: Окт. 31, 2023

Язык: Английский

Процитировано

4

Exploratory survey study on adjunctive use of medical cannabis for Gaucher disease DOI Open Access

Yehoshua Berman,

Robin J. Ely,

Yosef Y. Scher

и другие.

Rare Disease and Orphan Drugs Journal, Год журнала: 2024, Номер 3(3)

Опубликована: Авг. 23, 2024

Aims : Using an investigator-designed survey tool to confirm that adult patients with type 1 Gaucher disease (GD1) often self-prescribe cannabis products try alleviate symptoms such as lingering fatigue, chronic bone and joint pain, loss of energy, anxiety, depression persist despite enzyme replacement therapy (ERT) or substrate restriction (SRT). Additionally, explore whether patient reports symptom relief adverse side effects relate frequency duration use. Methods We conducted anonymous, cross-sectional questionnaire study elicit GD1 patient-reported experiences used they attributed their underlying disease. Eligible participants included individuals aged ≥ 18 years, regardless sex, gender, country residence, ethnicity, state health treatment status. The questions basic socio-demography (n = 9), GD diagnosis pre-treatment signs 16), information current 12), concurrent manifestations Parkinson’s 6), details use 24), perceived effect on 13), interest in participating future studies 2). Results: 159 adults (81.5% US) responded advertisements online sites informational posts advocacy group newsletters. most frequent were fatigue (83.8%), pain (79.7%), bleeding problems (73.0%). Hemostasis substantially improved, but achiness, anxiety persisted. Sixty-two respondents (39%) reported very heterogeneous There was a positive association between the severity persistent likelihood Cannabis users improvements muscle (84.3%), (82.4%), (70.6%), general achiness (66.7%). However, moderate extreme manifestations, breathing problems, memory loss, episodic dyscoordination more prevalent among inhaled than non-users. Conclusion: Our results justify further investigations determine efficacy safety specifically for patients. Although randomized controlled trials would be optimal, well-designed observational registry may practical approach. some reluctant talk openly doctors about cannabis, should routinely queried by primary care physicians specialists who, turn, must able provide informed guidance safety, dosage, potential interactions other medications is using.

Язык: Английский

Процитировано

1

Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy DOI Creative Commons
Sonia Burgaz, Elisa Navarro, Santiago Rodríguez-Carreiro

и другие.

Behavioral and Brain Functions, Год журнала: 2024, Номер 20(1)

Опубликована: Ноя. 1, 2024

The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ afforded neuroprotection in experimental models of Parkinson's disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties a PD model that also involves protein dysregulation, other key event pathogenesis.

Язык: Английский

Процитировано

0