OAR@UM Collection:https://www.um.edu.mt/library/oar/handle/123456789/235292024-03-29T15:44:14Z2024-03-29T15:44:14ZAdenosine A2A receptor antagonist treatment of Parkinson’s diseasePinna, AnnalisaSimola, NicolaMorelli, Micaelahttps://www.um.edu.mt/library/oar/handle/123456789/236442017-11-10T02:22:47Z2007-01-01T00:00:00ZTitle: Adenosine A2A receptor antagonist treatment of Parkinson’s disease
Authors: Pinna, Annalisa; Simola, Nicola; Morelli, Micaela
Abstract: Adenosine A2A receptors have a unique cellular and regional distribution in the basal ganglia (BG), being particularly concentrated in areas richly innervated by dopamine (DA) such as the caudateputamen, otherwise called striatum, and the globus pallidus. Adenosine A2A and DA D2 receptors are capable of forming functional heteromeric complexes and are colocalised in striatopallidal neurons. Based on the peculiar cellular and regional distribution of this receptor and in line with data showing that A2A receptor antagonists improve motor symptoms of Parkinson’s disease (PD) in animal models and in clinical trials, A2A receptor antagonists have emerged as an attractive nondopaminergic target to improve the motor deficits that characterise PD. Experimental data have also shown that A2A receptor antagonists are capable of exerting a neuroprotective effect and do not induce neuroplasticity phenomena that complicate long-term dopaminergic treatments. The present review will provide an updated summary of results reported in the literature concerning the biochemical characteristics and BG distribution of A2A receptors. We subsequently aim to examine the effects of adenosine A2A antagonists in rodent and primate models of PD and L-DOPA-induced dyskinesia. Finally, conclusive remarks will be made on the neuroprotective effects of A2A antagonists and on the translation of adenosine A2A receptor antagonists in the treatment of PD.2007-01-01T00:00:00ZEstrogen, neuroinflammation and neuroprotection in Parkinson’s disease : key role of neuron-glia crosstalkMarchetti, Biancahttps://www.um.edu.mt/library/oar/handle/123456789/236402017-11-10T02:22:28Z2007-01-01T00:00:00ZTitle: Estrogen, neuroinflammation and neuroprotection in Parkinson’s disease : key role of neuron-glia crosstalk
Authors: Marchetti, Bianca
Abstract: Post-menopausal estrogen deficiency is recognized as playing a pivotal role in the pathogenesis of a number of age-related diseases in women, such as osteoporosis, coronary heart disease and Alzheimer’s disease. There are also sexual differences in the progression of diseases associated with the nigrostriatal dopaminergic (DA) system, such as Parkinson’s disease (PD), a chronic progressive degenerative disorder characterized by the selective degeneration of mesencephalic dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). The mechanism(s) responsible for DA neuron degeneration in PD are still unknown, but oxidative stress and neuroinflammation are believed to play a pivotal role in nigrostriatal DA neuron demise. In addition, a complex interplay between genetic and environmental factors is believed to modulate the vulnerability of nigral DA neurons. Estrogen (E2) neuroprotective effects have been widely reported in a number of neuronal cell systems including nigrostriatal DA neurons, via both genomic and non-genomic effects. Besides other mechanisms, E2 modulation of astrocyte and microglia function in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD has recently emerged. Here we highlight E2 as a multifunctional hormone targeting the nigrostriatal DA system during health and disease with a particular focus on gender and E2 modulation of innate and adaptive immune responses as key factors involved in neuronal vulnerability. Special emphasis is given to the cardinal role of glia-neuron crosstalk directing neuroprotection vs neurodegneration and the role of E2 in switching astrocyte and microglia pro-inflammatory phenotype into a neuroprotective and anti-inflammatory state. Specifically, astrocyte and microglia response to the neurotoxin MPTP, and in particular the expression of pro-inflammatory mediators, vary according to estrogenic status with direct consequences for DA neuron survival, recovery and repair. The herein described estrogenic activation of glial anti-inflammatory and “protective” functions may provide a means to reduce the detrimental effects of neuroinflammation, while promoting cytokine activation of astroglial “pro-regenerative” functions. This mechanism might represent a compensatory/adaptive response to reduce neuronal vulnerability and/or to stimulate the repair process. These findings provide a new insight into the protective action of estrogen that may possibly contribute to the development of novel therapeutic treatment strategies for Parkinson’s disease.2007-01-01T00:00:00ZThe pathophysiology of motor thalamusPerea Bartolome, VictoriaLadera Fernandez, Valentinahttps://www.um.edu.mt/library/oar/handle/123456789/236302017-11-10T02:23:26Z2007-01-01T00:00:00ZTitle: The pathophysiology of motor thalamus
Authors: Perea Bartolome, Victoria; Ladera Fernandez, Valentina
Abstract: The thalamus is considered an important structure of sensitive pathways, and also intervenes in motor tasks. It receives multiple cortical and subcortical afferent fibers and the relations between their different nuclei are intense. After anatomic and functional study of the thalamic structure and its connections, we will analyze the different classifications and proposed subdivisions of the thalamic nuclear groups both in primates and humans. We will direct our study towards those aspects of the thalamus related to movement. The motor thalamus is described in most non-human primate studies as the thalamic region that receives subcortical afferent fibers from the basal ganglia and the cerebellum, and cortical fibers of the primary motor and pre-motor areas and these functions are also inferred to the human thalamus based on the cytoarchitectonic similarity between them. Later on, the pathological clinical aspects related to the motor thalamus are discussed. Disturbances or impairments in the coordination and course of movement, in muscular tone, and movement planning can be associated with injuries located in the motor thalamus and its connections. The research related to surgical procedures involving the thalamic structure for the treatment of impairments or disturbances of motion and movement are examined and will permit a comprehensive summary of the different mechanisms involved in the pathophysiology of the motor thalamus.2007-01-01T00:00:00ZIntroductionhttps://www.um.edu.mt/library/oar/handle/123456789/236272017-11-10T02:22:54Z2007-01-01T00:00:00ZTitle: Introduction
Abstract: Preface and contents for The Basal Ganglia Pathophysiology: Recent Advances 2007.2007-01-01T00:00:00Z