Cannabidiol biases A-CB receptor heteromer function by decoupling β-arrestin signaling from complex formation.

Cannabidiol (CBD), a phytocannabinoid with pleiotropic effects, exhibits complex mechanisms of action that remain incompletely understood, particularly its role as an allosteric modulator of G protein-coupled receptor (GPCR) heteromers. Among these, the adenosine A-cannabinoid CB receptor heteromer (AR-CBR) is a functionally relevant complex implicated in diverse physiological processes. This study aimed to characterize the modulatory effects of CBD on AR-CBR heteromers.

Machine Learning Approach to Select Small Compounds in Plasma as Predictors of Alzheimer's Disease.

This study employs a machine learning approach to identify a small-molecule-based signature capable of predicting Alzheimer's disease (AD). Utilizing metabolomics data from the plasma of a well-characterized cohort of 94 AD patients and 62 healthy controls; metabolite levels were assessed using the platform. Data preprocessing involved removing low-quality samples, selecting relevant biochemical groups, and normalizing metabolite data based on demographic variables such as age, sex, and fasting time.

Neuroprotective effects of G9a inhibition and cannabinoid receptor activation in Alzheimer's disease through a pharmacological approach.

Epigenetic alterations are key contributors to Alzheimer's disease (AD), driving age-related cognitive decline. This study explores the combined neuroprotective effects of G9a histone methyltransferase inhibition (via UNC0642) and cannabinoid receptor activation (CB1R: ACEA; CB2R: JWH133) in AD models. We used HEK-293T cells and hippocampal neurons to demonstrate that G9a inhibition selectively enhances CB1R-mediated ERK/cAMP signaling.

Cannabidiol as a multifaceted therapeutic agent: mitigating Alzheimer's disease pathology and enhancing cognitive function.

Background: Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has garnered significant interest due to its non-psychoactive nature and diverse receptor interactions.

Methods: This study employs in vitro and in vivo methodologies to validate CBD's potential as a treatment for Alzheimer's disease (AD) by addressing key hallmarks of the condition and promoting neuroprotective effects on spatial memory.

Results: Our findings demonstrate CBD's ability to decrease pTau and Aβ aggregation and to mitigate their axonal transport between cortical and hippocampal neurons.

Novel protocol for metabolomics data normalization and biomarker discovery in human tears.

Objectives: Human tear analysis holds promise for biomarker discovery, but its clinical utility is hindered by the lack of standardized reference values, limiting interindividual comparisons. This study aimed at developing a protocol for normalizing metabolomic data from human tears, enhancing its potential for biomarker identification.

Methods: Tear metabolomic profiling was conducted on 103 donors (64 females, 39 males, aged 18-82 years) without ocular pathology, using the AbsoluteIDQ™ p180 Kit for targeted metabolomics.

Novel Soluble Epoxide Hydrolase Inhibitor: Toward Regulatory Preclinical Studies.

Neuroinflammation is widely recognized as a key pathological hallmark of Alzheimer's disease (AD). Recently, inhibiting soluble epoxide hydrolase (sEH) has emerged as a promising therapeutic strategy for AD. sEH plays a pivotal role in neuroinflammation by hydrolyzing epoxyeicosatrienoic acids (EETs), which have anti-inflammatory and neuroprotective properties, into pro-inflammatory dihydroepoxyeicosatrienoic acids (DHETs).

Membrane Heteroreceptor Complexes as Second-Order Protein Modulators: A Novel Integrative Mechanism through Allosteric Receptor-Receptor Interactions.

Bioluminescence and fluorescence resonance energy transfer (BRET and FRET) together with the proximity ligation method revealed the existence of G-protein-coupled receptors, Ionotropic and Receptor tyrosine kinase heterocomplexes, e.g., A2AR-D2R, GABAA-D5R, and FGFR1-5-HT1AR heterocomplexes.

The Olfactory Trail of Neurodegenerative Diseases.

Alterations in olfactory functions are proposed as possible early biomarkers of neurodegenerative diseases. Parkinson's and Alzheimer's diseases manifest olfactory dysfunction as a symptom, which is worth mentioning. The alterations do not occur in all patients, but they can serve to rule out neurodegenerative pathologies that are not associated with small deficits.

Advancing Personalized Medicine by Analytical Means: Selection of Three Metabolites That Allows Discrimination between Glaucoma, Diabetes, and Controls.

This paper aimed at devising an intelligence-based method to select compounds that can distinguish between open-angle glaucoma patients, type 2 diabetes patients, and healthy controls. Taking the concentration of 188 compounds measured in the aqueous humour (AH) of patients and controls, linear discriminant analysis (LDA) was used to identify the right combination of compounds that could lead to accurate diagnosis. All possibilities, using the leave-one-out approach, were considered through ad hoc programming and in silico massive data production and statistical analysis.