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Investigación enfermedad de Parkinson, artículos, publicaciones científicas y noticias

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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Potential Alzheimer's, Parkinson's Cure Found In Century-old Drug

el . Publicado en Investigación Parkinson

ScienceDaily (Aug. 18, 2008) - A new study conducted by researchers at Children's Hospital & Research Center Oakland shows that a century-old drug, methylene blue, may be able to slow or even cure Alzheimer's and Parkinson's disease. Used at a very low concentration - about the equivalent of a few raindrops in four Olympic-sized swimming pools of water - the drug slows cellular aging and enhances mitochondrial function, potentially allowing those with the diseases to live longer, healthier lives. -

A paper on the methylene blue study, conducted by Hani Atamna, PhD, and a his team at Children's, was published in the March 2008 issue of the Federation of American Societies for Experimental Biology (FASEB) Journal. Dr. Atamna's research found that methylene blue can prevent or slow the decline of mitochondrial function, specifically an important enzyme called complex IV. Because mitochondria are the principal suppliers of energy to all animal and human cells, their healthy function is critical.

"The results are very encouraging," said Dr. Atamna. "We'd eventually like to try to prevent the physical and cognitive decline associated with aging, with a focus on people with Alzheimer's disease. One of the key aspects of Alzheimer's disease is mitochondrial dysfunction, specifically complex IV dysfunction, which methylene blue improves. Our findings indicate that methylene blue, by enhancing mitochondrial function, expands the mitochondrial reserve of the brain. Adequate mitochondrial reserve is essential for preventing age-related disorders such as Alzheimer's disease."

Also impressed is one of Dr. Atamna's co-authors, Bruce Ames, PhD, a senior scientist at Children's and world-renowned expert in nutrition and aging. "What we potentially have is a wonder drug." said Dr. Ames. "To find that such a common and inexpensive drug can be used to increase and prolong the quality of life by treating such serious diseases is truly exciting."

Methylene blue, first discovered in 1891, is now used to treat methemoglobinemia, a blood disorder. But because high concentrations of methylene blue were known to damage the brain, no one thought to experiment with low concentrations. Also, drugs such as methylene blue do not easily reach the brain.

Dr. Atamna's research is the first to show that low concentrations of the drug have the ability to slow cellular aging in cultured cells in the laboratory and in live mice. He believes methylene blue has the potential to become another commonplace low-cost treatment like aspirin, prescribed as a blood thinner for people with heart disorders.

Dr. Atamna's research, funded by the Bruce and Giovanna Ames Foundation, was conducted at Children's research institute and will continue when Dr. Atamna assumes a position as a professor of Neuroscience at The Commonwealth Medical College in Pennsylvania.


Journal reference:

  1. Atamna et al. Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. The FASEB Journal, 2007; 22 (3): 703 DOI: 10.1096/fj.07-9610com

Adapted from materials provided by Children's Hospital & Research Center at Oakland, via EurekAlert!, a service of AAAS.

Children's Hospital & Research Center at Oakland. "Potential Alzheimer's, Parkinson's Cure Found In Century-old Drug." ScienceDaily 18 August 2008. 20 August 2008 .

Un estudio demuestra que un fármaco puede frenar el avance del párkinson

el . Publicado en Investigación Parkinson

La investigación, en la que ha participado el hospital Clínico, siguió a 1.176 pacientes de 14 países y constató que el Azilect retrasa la progresión de la enfermedad, aunque no la cura.

LARA COTERA. Zaragoza
Aún no se puede curar la enfermedad de Parkinson, pero es posible frenar su avance. Un estudio en el que han participado 1.176 pacientes de 129 hospitales, uno de ellos el Clínico Universitario Lozano Blesa, ha demostrado que un fármaco llamado Azilect, cuyo principio activo es la rasagilina, puede retrasar la progresión de este mal.
Las conclusiones detalladas de este importantísimo avance para 4 millones de pacientes en el mundo y más de 2.000 en Aragón se presentarán el próximo 26 de agosto en Madrid en el XII Congreso de la European Federation of Neurological Societies (EFN). No obstante, los coordinadores principales del estudio ya han comunicado a los investigadores de los centros sanitarios participantes (ubicados en 14 países diferentes) que se ha constatado que el medicamento es eficaz.
El neurólogo e investigador del Hospital Clínico Lozano Blesa, Javier López del Val, ha sido uno de los receptores de la noticia, que abre un campo de oportunidades para los afectados y, en especial, para quienes sufren la enfermedad en un estadio inicial.
"Es una noticia extraordinaria. No sabemos todavía cuál es el origen exacto del párkinson. Sí que conocemos que pueden influir la genética o los tóxicos ambientales, y por eso dar con un remedio que frene su avance es lo que llevamos años buscando", explica López del Val.

Proyecto ADAGIO

El Azilect es un fármaco de la empresa Teva Pharmaceutical Industries Ltd. Hace tiempo que se utiliza en pacientes de párkinson, aunque no para este fin. En principio, nació como un amplificador de la eficacia del tratamiento principal con dopamina, ya que mejoraba los síntomas.
Fue después cuando se impulsó el proyecto ADAGIO (Atenuation of Disease progression with Azilect Given Once Daily). Se trata de un estudio que ha seguido a dos grupos de pacientes, todos ellos precoces y no tratados.
A un primer grupo se le empezó a tratar de manera temprana, dándoles 1 miligramo o 2 al día durante 72 semanas. El otro sistema, de inicio tardío, consistía en que el segundo grupo tomara placebo durante 36 semanas y, después, ingiriese durante otras tantas semanas rasagilina a diario (entre 1 y 2 mg). El estudio concluyó hace cuatro meses y desde entonces se han estado analizando los resultados.
"Con los pacientes que participaban desde el Clínico nos dimos cuenta enseguida de que unos evolucionaban mucho mejor que otros", recuerda el doctor López del Val. "Es de esas ocasiones en las que lo notas, sabes que algo está funcionando de verdad", añade.
El fármaco está en el mercado y otro de los puntos más positivos que ha desvelado la investigación es que se ha demostrado que no tiene casi efectos secundarios. "Es decir, nuestros pacientes tienen mucho que ganar y muy poco que perder. No logramos que los síntomas regresen, pero sí que se mantengan", explica.
Por eso, las principales beneficiadas van a ser aquellas personas a los que se les acabe de diagnosticar y la enfermedad aún no les haya causado mermas considerables.
López del Val celebra además este nuevo paso en la lucha contra el párkinson. "Hace 26 años, los pacientes a los que llevabamos tratando 6 o 8 años estaban muy deteriorados. Ahora, por ejemplo, hay personas a las que las diagnosticamos hace 20 años y están en disposición de seguir luchando contra este mal en buenas condiciones", concreta.
El párkinson es un trastorno cerebral progresivo que causa temblores, lentitud de movimientos y rigidez muscular. En estos pacientes, las células que producen la dopamina empiezan a morir, algo trágico, porque precisamente la dopamina actúa como neurotransmisor. Es decir, es una sustancia química que permite a las células nerviosas comunicarse entre sí. Cuando estas fallan, los pacientes pierden la capacidad de controlar sus movimientos.
Sin embargo, la rasagilina es un inhibidor que bloquea la monoaminooxiadasa B, una enzima que degrada la dopamina. Los pacientes que la toman consiguen que aumente la concentración de dopamina en el cerebro y vuelvan a dominar sus movimientos.

Hsp104 antagonizes α-synuclein aggregation and reduces dopaminergic degeneration in a rat model of Parkinson disease

el . Publicado en Investigación Parkinson

Parkinson disease (PD) is characterized by dopaminergic neurodegeneration and intracellular inclusions of α-synuclein amyloid fibers, which are stable and difficult to dissolve. Whether inclusions are neuroprotective or pathological remains controversial, because prefibrillar oligomers may be more toxic than amyloid inclusions. Thus, whether therapies should target inclusions, preamyloid oligomers, or both is a critically important issue. In yeast, the protein-remodeling factor Hsp104 cooperates with Hsp70 and Hsp40 to dissolve and reactivate aggregated proteins. Metazoans, however, have no Hsp104 ortholog. Here we introduced Hsp104 into a rat PD model. Remarkably, Hsp104 reduced formation of phosphorylated α-synuclein inclusions and prevented nigrostriatal dopaminergic neurodegeneration induced by PD-linked α-synuclein (A30P). An in vitro assay employing pure proteins revealed that Hsp104 prevented fibrillization of α-synuclein and PD-linked variants (A30P, A53T, E46K). Hsp104 coupled ATP hydrolysis to the disassembly of preamyloid oligomers and amyloid fibers composed of α-synuclein. Furthermore, the mammalian Hsp70 and Hsp40 chaperones, Hsc70 and Hdj2, enhanced α-synuclein fiber disassembly by Hsp104. Hsp104 likely protects dopaminergic neurons by antagonizing toxic α-synuclein assemblies and might have therapeutic potential for PD and other neurodegenerative amyloidoses.

Articulo completo

New insight into what freezes Parkinson's patients and drives drug addicts

el . Publicado en Investigación Parkinson

 

CHICAGO -- Parkinson's disease and drug addiction are polar opposite diseases, but both depend upon dopamine in the brain. Parkinson's patients don't have enough of it; drug addicts get too much of it. Although the importance of dopamine in these disorders has been well known, the way it works has been a mystery.

New research from Northwestern University's Feinberg School of Medicine has revealed that dopamine strengthens and weakens the two primary circuits in the brain that control our behavior. This provides new insight into why a flood of dopamine can lead to compulsive, addictive behavior and too little dopamaine can leave Parkinson's patients frozen and unable to move.

"The study shows how dopamine shapes the two main circuits of the brain that control how we choose to act and what happens in these disease states, " said D. James Surmeier, lead author and the Nathan Smith Davis Professor and chair of physiology at the Feinberg School. The paper is published in the August 8 issue of the journal Science.

These two main brain circuits help us decide whether to act out a desire or not. For example, do you get off the couch and drive to the store for an icy six-pack of beer on a hot summer night, or just lay on the couch?

One circuit is a "stop" circuit that prevents you from acting on a desire; the other is a "go" circuit that provokes you to action. These circuits are located in the striatum, the region of the brain that translates thoughts into actions.

In the study, researchers examined the strength of synapses connecting the cerebral cortex, the region of the brain involved in perceptions, feelings and thought, to the striatum, home of the stop and go circuits that select or prevent action.

Scientists electrically activated the cortical fibers to simulate movement commands and boosted the natural level of dopamine. What happened next surprised them. The cortical synapses connecting to the "go" circuit became stronger and more powerful. At the same time, dopamine weakened the cortical connections in the "stop" circuit.

"This could be what underlies addiction," Surmeier said. "Dopamine released by drugs leads to abnormal strengthening of the cortical synapses driving the striatal 'go' circuits, while weakening synapses at opposing 'stop' circuits. As a result, when events associated with drug taking – where you took the drug, what you were feeling – occur, there is an uncontrollable drive to go and seek drugs."

"All of our actions in a healthy brain are balanced by the urge to do something and the urge to stop," Surmeier said. "Our work suggests that it is not just the strengthening of the brain circuits helping select actions that is critical to dopamine's effects, it is the weakening of the connections that enable us to stop as well. "

In the second part of the experiment, scientists created an animal model of Parkinson's disease by killing dopamine neurons. Then they looked at what happened when they simulated cortical commands to move. The result: the connections in the "stop" circuit were strengthened, and the connections in the "go" circuit were weakened.

"The study illuminates why Parkinson's patients have trouble performing everyday tasks like reaching across a table to pick up a glass of water when they are thirsty," Surmeier said.

Surmeier explained the phenomenon using the analogy of a car. "Our study suggests that the inability to move in Parkinson's disease is not a passive process like a car running out of gas," he said. "Rather, the car doesn't' move because your foot is jammed down on the brake. Dopamine normally helps you adjust the pressure on the brake and gas pedals. It helps you learn that when you see a red light at an intersection, you brake and when the green light comes on, you take your foot off the brake and depress the gas pedal to go. Parkinson's disease patients, who have lost the neurons that release dopamine, have their foot perpetually stuck on the brake."

Understanding the basis for these changes in brain circuitry moves scientists closer to new therapeutic strategies for controlling these brain disorders and other involving dopamine like schizophrenia, Tourette's syndrome and dystonia.

Contact: Marla Paul
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312-503-8928
Northwestern University

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