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Cannabinoid Synuclein

Cristina Palomo-Garo, Yolanda Gómez-Gálvez, Concepción García, Javier Fernández-Ruiz
Most of cases of Parkinson's disease (PD) have a sporadic origin, with their causes mostly unknown, although overexposure to some environmental factors has been found to occur in some cases. Other forms of parkinsonism are the consequence of dominant or recessive mutations in specific genes, e.g. α-synuclein, parkin and, more recently, leucine-rich repeat kinase 2 (LRRK2), whose G2019S mutation represents the most prevalent form of late-onset, autosomal dominant familial PD. A transgenic mouse model expressing the G2019S mutation of LRRK2 is already available and apparently may represent a valuable experimental model for investigating PD pathogenesis and novel treatments...
August 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Samantha Mancino, Aurelijus Burokas, Javier Gutiérrez-Cuesta, Miriam Gutiérrez-Martos, Elena Martín-García, Mariangela Pucci, Anastasia Falconi, Claudio D'Addario, Mauro Maccarrone, Rafael Maldonado
An increasing perspective conceptualizes obesity and overeating as disorders related to addictive-like processes that could share common neurobiological mechanisms. In the present study, we aimed at validating an animal model of eating addictive-like behavior in mice, based on the DSM-5 substance use disorder criteria, using operant conditioning maintained by highly palatable chocolate-flavored pellets. For this purpose, we evaluated persistence of food-seeking during a period of non-availability of food, motivation for food, and perseverance of responding when the reward was associated with a punishment...
November 2015: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Alejandro López-Jiménez, Nicole A R Walter, Elena Giné, Ángel Santos, Victor Echeverry-Alzate, Kora-Mareen Bühler, Pedro Olmos, Stéphanie Giezendanner, Rosario Moratalla, Lluis Montoliu, Kari J Buck, Jose Antonio López-Moreno
α-Synuclein (α-syn) protein and endocannabinoid CB1 receptors are primarily located in presynaptic terminals. An association between α-syn and CB1 receptors has recently been established in Parkinson's disease, but it is completely unknown whether there is an association between these two proteins in alcohol addiction. Therefore, we aimed to examine the α-syn mRNA transcript and protein expression levels in the prefrontal cortex, striatum, amygdala and hippocampus. These brain regions are the most frequently implicated in alcohol and other drug addiction...
June 2013: Synapse
Claudia Maria Miranda Santos
Although researchers are pursuing "disease modifying" medications to slow or stop Parkinson's disease (PD) progression, a myriad of agents with protective properties in cell cultures and animal models have yielded few treatments in clinical practice. Developing safe and effective treatments with disease-modifying/neuroprotective mechanisms of action and identifying patients in the pre-motor phase will be a challenge. The implication of tyrosine hydroxylase (TH), the enzyme that catalyzes the formation of L-3,4-dihydroxyphenylalanine, in the pathogenesis of PD at different levels makes it a promising candidate for developing efficient treatment based on correcting or bypassing the enzyme deficiency...
June 1, 2012: CNS & Neurological Disorders Drug Targets
Posung Jeon, Sungjun Yang, Hojoong Jeong, Hyun Kim
Cannabinoids have been proposed to possess neuroprotective properties; though their mechanism of action remains contentious, they are posited to prevent neurodegenerative disorders, including Parkinson's disease, the pathogenesis of which has not been established. Recent studies have demonstrated that induction of proteasomal dysfunction in animal models results in a phenotype similar to Parkinson's disease. Here, we investigated the neuroprotective function of a synthetic cannabinoid-receptor agonist (WIN55...
June 2011: Anatomy & Cell Biology
Isidre Ferrer, Anna Martinez, Rosa Blanco, Ester Dalfó, Margarita Carmona
Parkinson disease (PD) is no longer considered a complex motor disorder characterized by parkinsonism but rather a systemic disease with variegated non-motor deficits and neurological symptoms, including impaired olfaction, sleep disorders, gastrointestinal and urinary abnormalities and cardiovascular dysfunction, in addition to other symptoms and signs such as pain, depression and mood disorders. Many of these alterations appear before or in parallel with motor deficits and then worsen with disease progression...
May 2011: Journal of Neural Transmission
Alexander Kurz, Kay L Double, Isabel Lastres-Becker, Alessandro Tozzi, Michela Tantucci, Vanessa Bockhart, Michael Bonin, Moisés García-Arencibia, Silke Nuber, Falk Schlaudraff, Birgit Liss, Javier Fernández-Ruiz, Manfred Gerlach, Ullrich Wüllner, Hartmut Lüddens, Paolo Calabresi, Georg Auburger, Suzana Gispert
BACKGROUND: Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms...
July 7, 2010: PloS One
Moisés García-Arencibia, Concepción García, Alexander Kurz, José A Rodríguez-Navarro, Suzana Gispert-Sáchez, Maria A Mena, Georg Auburger, Justo García de Yébenes, Javier Fernández-Ruiz
This study was designed to examine the type of changes experienced by the CB1 receptor, a key element of the cannabinoid signaling system, in the basal ganglia of different mouse mutants generated by deletion of specific genes associated with the development of Parkinson's disease in humans [PARK1 (alpha-synuclein), PARK2 (parkin) or PARK6 (PINK1)]. We observed that CB1 receptor-mRNA levels were significantly reduced in the caudate-putamen in the three models under examination when animals were analyzed at early phases (< or = 12 months of age)...
2009: Journal of Neural Transmission. Supplementum
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