Prolactinomas, the most common pituitary-secreting adenomas, can be effectively treated with dopamine D2 receptor (D2R) agonists. However, a subset of them (∼20%) are resistant to dopamine-based therapies and require extirpation. The molecular mechanisms underlying their escape from dopaminergic regulation are not fully elucidated and may include alterations in D2R signaling.
View Article and Find Full Text PDFThe orphan G protein-coupled receptor 37 (GPR37), widely associated with Parkinson's disease (PD), undergoes proteolytic processing under physiological conditions. The N-terminus domain is proteolyzed by a disintegrin and metalloproteinase 10 (ADAM-10), which generates various membrane receptor forms and ectodomain shedding (ecto-GPR37) in the extracellular environment. We investigated the processing and density of GPR37 in several neurodegenerative conditions, including Lewy body disease (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD).
View Article and Find Full Text PDFObjectives: Cannabidiol (CBD) is a phytocannabinoid with great potential in clinical applications. The mechanism(s) of action of CBD require further investigation. Previous studies suggested that adenosine A receptors (ARs) could play a role in CBD-induced effects.
View Article and Find Full Text PDFAdenosine modulates neurotransmission through inhibitory adenosine A receptors (ARs) and stimulatory A receptors (ARs). These G protein-coupled receptors are involved in motor function and related to neurodegenerative diseases such as Parkinson's disease (PD). An autosomal-recessive mutation (G279S) within the transmembrane helix (TM) 7 of AR (AR) has been associated with the development of early onset PD (EOPD).
View Article and Find Full Text PDFGPR37 is an orphan G protein-coupled receptor (GPCR) implicated in several neurological diseases and important physiological pathways in the brain. We previously reported that its long N-terminal ectodomain undergoes constitutive metalloprotease-mediated cleavage and shedding, which have been rarely described for class A GPCRs. Here, we demonstrate that the protease that cleaves GPR37 at Glu167↓Gln168 is a disintegrin and metalloprotease 10 (ADAM10).
View Article and Find Full Text PDFObjective: α-Synuclein has been studied as a potential biomarker for Parkinson's disease (PD) with no concluding results. Accordingly, there is an urgent need to find out reliable specific biomarkers for PD. GPR37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile parkinsonism.
View Article and Find Full Text PDFIn recent years, new drug discovery approaches based on novel pharmacological concepts have emerged. Allosteric modulators, for example, target receptors at sites other than the orthosteric binding sites and can modulate agonist-mediated activation. Interestingly, allosteric regulation may allow a fine-tuned regulation of unbalanced neurotransmitter' systems, thus providing safe and effective treatments for a number of central nervous system diseases.
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