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Investigación enfermedad de Parkinson, artículos, publicaciones científicas y noticias

Discovery Of Protein That Regulates Gene Critical To Dopamine-Releasing Brain Cells

el . Publicado en Investigación Parkinson

Researchers have identified a protein they say appears to be a primary player in maintaining normal functioning of an important class of neurons - those brain cells that produce, excrete and then reabsorb dopamine neurotransmitters. These molecules command numerous body functions, ranging from management of behavior and mood to control of movement, and one day may hold the key to why and how some people develop Parkinson's and other brain diseases.
In the Journal of Neuroscience, the scientists say that this protein, which they call the Nurr-1 interacting protein (NuIP), interacts with, and helps regulate the activity of the Nurr1 gene. That gene has long been known to be essential to development and maintenance of dopaminergic neurons.
Efforts to control Nurr-1 have been underway by pharmaceutical drug developers, because these neurons are the ones that die in Parkinson's disease and which are, conversely, over-active in schizophrenia. Now NuIP may also provide a good drug target for these and other neurological disorders caused by faulty dopamine transmission, says the study's lead investigator, Howard J. Federoff, M.D., Ph.D., Executive Vice President for Health Sciences and Executive Dean of the School of Medicine at Georgetown University Medical Center.
"We do not know yet whether this is true, but one can speculate that small molecules that may either facilitate, stabilize, or otherwise regulate the action of NuIP on Nurr1 may be relevant in a therapeutic context," says Federoff, a neuroscientist who did much of this research at the University of Rochester School of Medicine and Dentistry before coming to Georgetown in 2007. His three other co-authors are from Rochester.
In this study, the researchers specifically set out to find potential "partners" of Nurr1 because no molecule had yet been found that could positively activate the Nurr1 gene or the protein receptor it produces. Crystal structures of the Nurr1 receptor show it to have an area where another protein could bind to it, but this "domain" is too small for usual binding partners, such as steroids.
Using a library of potential molecules in laboratory samples of brain cells from a developing mouse, the researchers identified a new family of gene products that interacts with and regulates the activity of Nurr1. These gene products are all derived from the NuIP gene.
They then discovered that loss of NuIP function led to decreased numbers of cells in culture and to a decreased expression of the dopamine transporter on these neurons.
The mechanism underlying the ability of NuIP to positively regulate the activity of Nurr1 is not yet clear, but the researchers suspect that "as yet unknown upstream signals impinge on NuIP which, in turn, instructs Nurr1 to become activated and thus facilitates the expression of a set of genes involved in dopamine neuron phenotypic maturation," Federoff says. "That means they become more like a dopamine neuron which manufactures, releases, and the takes up the neurotransmitter."
"The relevance of NuIP to Parkinson's disease has not been established but it is tempting to speculate that it participates in the maintenance of the mature phenotype of midbrain dopaminergic neurons which are rendered vulnerable in this neurological disease," Federoff says.

Source: Karen Mallet
Georgetown University Medical Center
Original article posted on Medical News Today.

Las Verdaderas Celulas madre del cerebro adulto

el . Publicado en Investigación Parkinson

Las células madre adultas se originan en una parte del cerebro diferente de la que comúnmente se había venido señalando, y con la estimulación adecuada pueden producir nuevas células cerebrales para reemplazar a las perdidas por enfermedades o lesiones cerebrales, según demuestra un estudio realizado por científicos de la Universidad de California en Irvine.

Las evidencias muestran de manera muy sólida que las verdaderas células madre en el cerebro de los mamíferos son las células ependimarias que forran los ventrículos en el cerebro y en la médula espinal, en vez de las células en la zona subventricular, como creían anteriormente los biólogos.
Los ventrículos cerebrales son cámaras huecas llenas de fluido que sostienen al tejido cerebral, y están cubiertos por una capa de estas células ependimarias.
Es crucial conocer la fuente de las células cuando se desarrollan terapias basadas en células madre. Además, el saber que estas células normalmente durmientes pueden ser inducidas a realizar la división celular abre el camino hacia terapias futuras en las que las propias células madre del paciente produzcan nuevas células cerebrales para tratar enfermedades y lesiones neurológicas, como por ejemplo el mal de Parkinson, los derrames cerebrales o las heridas neurológicas provocadas por accidentes y otras causas no naturales.

"Con tal terapia, sabríamos a qué células en el cuerpo activar, y su descendencia tendría todas las propiedades necesarias para reemplazar a las células dañadas o ausentes", explica Darius Gleason, autor principal del estudio. "Este es un enfoque muy prometedor de la terapia con células madre".
Las células madre son las "células primordiales" que producen todas las demás células especializadas del cuerpo humano. Si los científicos pudieran controlar la producción y diferenciación de las células madre, serían capaces de utilizarlas para reemplazar los tejidos dañados.
Uno de los objetivos de la investigación en células madre es mejorar el transplante de las mismas. El proceso usual pasa por inyectar en el cuerpo del paciente células sanas que pueden encajar genéticamente con las del paciente o no. El transplante de células madre con diferencias genéticas importantes requiere el empleo de fármacos para evitar que el cuerpo rechace el tratamiento.
Pero si se puede trabajar habitualmente con las células madre del propio paciente, se eliminaría la necesidad de transplantes y de fármacos inmunosupresores, lo que sería sin duda una mejor alternativa.

Articulo original:

Testamento vital

el . Publicado en Investigación Parkinson

Argumento sensible, que enfrenta conciencias y necesidades, pacientes y médicos, enfermos y cuidadores.

Nadie se queda insensible delante de esta decisión.

Para contribuir al debate tomamos como punto de partida para la reflexión un articulo de BiblioMed.

image

Un testamento es un documento con indicaciones anticipadas que realiza una persona en situación de lucidez mental para que sea tenido en cuenta cuando, a causa de una enfermedad o de otro evento, ya no le sea posible expresar su voluntad. La novedad que más trascendió en los últimos tiempos escapa al ámbito económico y se centra en lo que la persona que testa define como muerte digna. A veces, los deseos de quien testa van en contra de legislaciones o deseos de familiares cercanos. ¿Qué se hace entonces?.

Lo más concretamente controvertido de este tipo de documentos es lo que concierne e involucra a la asistencia y tratamiento médico a practicarse sobre un paciente que se encuentra bajo una condición física o mental incurable o irreversible y sin expectativas de curación.

En general, las instrucciones de estos testamentos se aplican sobre una condición terminal, bajo un estado permanente de inconsciencia o sobre un daño cerebral irreversible que, más allá de la conciencia, no posibilite que la persona recupere la capacidad para tomar decisiones y expresar sus deseos en el futuro. Es allí donde un testamento vital insta a que el tratamiento a practicarse se limite a las medidas necesarias para mantener confortable, lúcido, aliviando del dolor (incluyendo los que puedan ocurrir como consecuencia de la suspensión o interrupción del tratamiento).

Una tema para el debate

Extracellular dopamine induces the oxidative toxicity of SH-SY5Y cells

el . Publicado en Investigación Parkinson

Yuhua Jiang 1 2, Lin Pei 1, Shupeng Li 1, Min Wang 1, Fang Liu 1 3 *

1Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, University of Toronto, Toronto, Ontario, Canada M5T 1R8
2Department of Radiation Oncology, Qilu Hospital, Shandong University, Ji-Nan 250012, People's Republic of China
3Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8

email: Fang Liu (Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.)

*Correspondence to Fang Liu, Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, Ontario, Canada M5T 1R8

Abstract

Dopamine-induced neuronal cytotoxicity has been proposed as a leading pathological mechanism underlying many neuronal degenerative disorders including Parkinson disease. Various hypotheses have been proposed including oxidative stress and dopamine (DA)-induced intracellular signal disorder via DA D1 and D2 receptors. The exact mechanism involved in this process is far from clear. In this study, employing a neuronal blastoma cell line, SH-SY5Y, we tried to elucidate the roles of these different suggested mechanisms in this pathological process. The results showed that DA induced cell toxicity in a dose- and time-dependent way. Selective D1 and D2 DA receptor antagonist could not block the cytotoxic effects, whereas reductive reagent ascorbic acid but not GSH could effectively rescue the cell death, suggesting that DA-induced cell toxicity was caused by an extracellular oxidative stress. This was further supported by the enhancing effects of DA transporter blocker, GBR, which could increase the cell death when pretreated. Finally, ascorbic acid could also protect SY5Y cells from DA-induced cellular apoptotic signal changes including PARP and P53. Our studies suggested that DA exerted its cytotoxic effects via an extracellular metabolism, whereas intracellular transportation could reduce its oxidative stress. Cytotoxicity effects induced by extracellular DA could be protected by reductive agents as ascorbic acid. These results help to broaden our understanding of the mechanisms of DA-induced cell death and may provide potentially therapeutical alternative for the neurodegenerative disorders. Synapse 62:797-803, 2008. © 2008 Wiley-Liss, Inc.

LSUHSC Research Reports New Method To Protect Brain Cells From Diseases Like Alzheimer's & Parkinson's disease

el . Publicado en Investigación Parkinson

New research led by Chu Chen, PhD, Associate Professor of Neuroscience at LSU Health Sciences Center New Orleans, provides evidence that one of the only naturally occurring fatty acids in the brain that has the ability to interact with the receptors originally identified as the targets of THC (the psychoactive component of marijuana) can help to protect brain cells from neurodegenerative diseases like Alzheimer's and Parkinson's. Published in the Journal of Biological Chemistry, the research focuses on the cellular and molecular mechanisms of inflammation, specifically the role these relatively recently discovered endogenous cannabinoids can play in the control of COX-2 and other cyclooxygenases. COX-2 is a key player in neuroinflammation and has been implicated in the development of neurodegenerative diseases and worsening of damage from such insults as traumatic brain injury and stroke.
Chen and research associate Jian Zhang show that endocannabinoid 2-arachidonoylglycerol (2-AG) functions as an endogenous COX-2 inhibitor, turning off the production of COX-2 which normally goes into overdrive in response to pro-inflammatory and certain types of toxic stimuli, resulting in the injury or death of brain cells. The researchers also revealed the specific signaling pathways that regulate the 2-AG suppression of COX-2. The paper, Endocannabinoid 2-Arachidonoylglycerol Protects Neurons by Limiting COX-2 Elevation, is available online at http://www.jbc.org/.
"Our findings provide a basis for opening up new therapeutic approaches to protect neurons from inflammation and toxicity-induced neurodegeneration," notes Chen. "Selective COX-2 inhibitors were thought to be a promising medicine in treating neurodegenerative diseases, stroke, cancers and inflammation-related diseases like arthritis; however, the occurrence of a series of cardiovascular complications in patients receiving COX-2 inhibitors has led to their recent withdrawal from the market and limits on their usages. Our research has shown that the use of endogenous cannabinoid 2-AG may avoid such side effects. Therefore, elevation of endogenous 2-AG levels by facilitating its production, inhibiting its decomposition, or directly supplying 2-AG may result in treatment advances to prevent the devastation of disorders like stroke, Alzheimer's and traumatic brain injury."
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Article adapted by Medical News Today from original press release.
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