Cannabinoid CB receptors (CBR) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson's disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, MPP, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake MPP that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of MPP showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the CBR antagonist, SR141716, afforded an almost full neuroprotection in CBR-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing CB/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of CBR, GPR55, and their heteromers as targets to afford PD-related neuroprotection.
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http://dx.doi.org/10.1007/s12035-019-1495-4 | DOI Listing |
Mol Cell Biochem
December 2024
Department XIII Infectious Diseases-Parasitology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania.
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Department of Research and Development, First Floor, Molecules Biolabs Private Limited, Commercial Building Kinfra, 3/634Konoor Road, Muringur, Vadakkummuri, Koratty, Mukundapuram, Thrissur, Kerala, 680309, India.
Palmitoylethanolamide (PEA) is emerging as a promising therapeutic agent for neuropathic and other pain-related conditions. This naturally occurring fatty acid has drawn interest because of its ability to regulate pain and inflammation. Initially identified in food sources, PEA has been the subject of extensive research to elucidate its properties, efficacy, and clinical applications.
View Article and Find Full Text PDFElife
December 2024
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Parkinson's disease (PD) is a multifactorial disease caused by irreversible progressive loss of dopaminergic neurons (DANs). Recent studies have reported the successful conversion of astrocytes into DANs by repressing polypyrimidine tract binding protein 1 (PTBP1), which led to the rescue of motor symptoms in a chemically-induced mouse model of PD. However, follow-up studies have questioned the validity of this astrocyte-to-DAN conversion model.
View Article and Find Full Text PDFJ Cell Biol
February 2025
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
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View Article and Find Full Text PDFJ Geriatr Psychiatry Neurol
December 2024
Laboratory for Early Markers of Neurodegeneration (LEMON), Center for the Study of Movement, Cognition, and Mobility (CMCM), Tel Aviv Sourasky Medical Center, Neurological Institute, Tel Aviv, Israel.
Switching, a critical executive function, can manifest as task switching (TS) or response switching (RS). Although TS impairments in Parkinson's disease (PD) are well-studied, RS, especially in contexts requiring adaptive behavior to external or internal cues, is less explored. This study evaluated the impact of PD on RS under exogenous and endogenous cueing.
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