Investigadores
del Instituto de Salud Nacional de Estados Unidos han desvelado que una
importante proteína vinculada a los casos de inicio temprano del párkinson,
Parkin, regula la manera en que las células toman y procesan las grasas de la
dieta en el cuerpo humano.
El
estudio, publicado en la edición electrónica de Journal of Clinical Investigation, sugiere que un defecto en Parkin puede contribuir indirectamente
al desarrollo de algunos casos de inicio precoz del párkinson al variar la
cantidad y los tipos de grasa en el cuerpo humano. Las mutaciones de esta
proteína se dan en el 37% de los casos de quienes padecen la enfermedad a los
20 años, no obstante, los ratones con defectos en esta proteína no muestran
signos obvios de la enfermedad.
“Este
avance significa que para entender el párkinson no hay que centrarse
necesariamente en el cerebro”, apunta el autor principal del estudio, Michael
Sack, jefe del Laboratorio de Biología Mitocondrial en Síndromes Cardiometabólicos.
El
equipo de trabajo observó que los ratones con Parkin defectuosa no ganaban peso
al llevar a cabo una dieta de laboratorio alta en grasas, como solía ocurrir habitualmente.
Y al examinar varios órganos de estos animales constataron que las células
contenían niveles bajos de ciertas proteínas trasportadoras de grasa. Por el
contrario, los ratones normales que habían consumido la misma dieta tenían
niveles altos de aquéllas y también de Parkin, lo que sugiere que ésta proteína
está implicada en el trasporte de la grasa.
Posteriormente,
analizando las células sanguíneas de pacientes del centro que ha realizado la
investigación, los autores comprobaron que el patrón murino se repetía en
humanos y que las células de las personas con mutaciones en Parkin tenían menos
facilidad para absorber las grasas.
“Las
células cerebrales se destruyen durante el transcurso de la enfermedad y la
región conocida como la sustancia negra controla el movimiento y a la vez tiene
otras funciones. Las neuronas de esta parte del cerebro son extremadamente
activas. Cada una tiene alrededor de 300 000 conexiones y transmiten
información constantemente. Estas neuronas requieren un buen soporte en sus
membranas de grasa y colesterol. Si la grasa “buena” no está disponible, la
integridad de la célula disminuirá y será más propensa a causar daño”, explica
Sack.
Protein linked to Parkinson's disease may regulate fat metabolism
National Institutes of Health researchers have found
that Parkin, an important protein linked with some cases of early-onset
Parkinson's disease, regulates how cells in our bodies take up and process
dietary fats.
Parkinson's disease is a complex, progressive, and currently incurable neurological disorder characterized by shaking, stiffness, slowed movement, and impaired balance. Parkinson's primarily affects people over 50, but in about 5 to10 percent of cases it occurs in people as young as their 20s. This form of the disease, which affects actor, author, and Parkinson's activist Michael J. Fox, is known as early-onset Parkinson's.
Parkin mutations are present in as many as 37 percent of early-onset Parkinson's cases. However, laboratory mice with defective Parkin do not display obvious signs of the disease.
This preliminary study, which appears online in the Journal of Clinical Investigation on Aug. 25, suggests defective Parkin may indirectly contribute to the development of some early-onset Parkinson's by changing the amount and types of fat in people's bodies.
"This discovery shows that the clues to understand Parkinson's disease may not necessarily be in the brain," said study leader Michael Sack, M.D., chief of the Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes at the NIH's National Heart, Lung, and Blood Institute.
The research team, composed of scientists from the NHLBI and the NIH's National Institute of Neurological Disorders and Stroke, observed that mice with defective Parkin did not gain weight in response to a high-fat laboratory diet, as regular mice typically do.
Parkinson's disease is a complex, progressive, and currently incurable neurological disorder characterized by shaking, stiffness, slowed movement, and impaired balance. Parkinson's primarily affects people over 50, but in about 5 to10 percent of cases it occurs in people as young as their 20s. This form of the disease, which affects actor, author, and Parkinson's activist Michael J. Fox, is known as early-onset Parkinson's.
Parkin mutations are present in as many as 37 percent of early-onset Parkinson's cases. However, laboratory mice with defective Parkin do not display obvious signs of the disease.
This preliminary study, which appears online in the Journal of Clinical Investigation on Aug. 25, suggests defective Parkin may indirectly contribute to the development of some early-onset Parkinson's by changing the amount and types of fat in people's bodies.
"This discovery shows that the clues to understand Parkinson's disease may not necessarily be in the brain," said study leader Michael Sack, M.D., chief of the Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes at the NIH's National Heart, Lung, and Blood Institute.
The research team, composed of scientists from the NHLBI and the NIH's National Institute of Neurological Disorders and Stroke, observed that mice with defective Parkin did not gain weight in response to a high-fat laboratory diet, as regular mice typically do.
When the researchers examined
several organs of the Parkin-defective mice, they noticed that the cells
contained low levels of certain proteins that transport fat in the body. In
contrast, normal mice that were fed the same high-fat diet had high levels of
these fat-carrying proteins, as well as high levels of Parkin, suggesting that
Parkin is involved in fat transportation.
The researchers saw a similar pattern when they analyzed blood cells from patients enrolled at the NIH Parkinson's Clinic. In lab tests, cells from people with Parkin mutations had less ability to absorb fat. These results provide evidence that the findings could be relevant in humans.
As to how fat may be important in Parkinson's, Dr. Sack notes that the brain cells destroyed during the course of the disease are found in a region called the substantia nigra, which controls movement, among other roles. "The neurons in this part of the brain are extremely active. Each one has over 300,000 connections and is continuously transmitting information," he said. "These neurons require good support in the form of their fat and cholesterol membrane. If the right types of fat aren't available, then cell integrity will be sub-par and they could be prone to damage."
Dr. Sack and his colleagues plan some early-stage clinical studies on the connection between fat metabolism and Parkinson's. They will continue working with the NIH Parkinson's Clinic and encourage patients to participate in the research as it moves forward.
The researchers saw a similar pattern when they analyzed blood cells from patients enrolled at the NIH Parkinson's Clinic. In lab tests, cells from people with Parkin mutations had less ability to absorb fat. These results provide evidence that the findings could be relevant in humans.
As to how fat may be important in Parkinson's, Dr. Sack notes that the brain cells destroyed during the course of the disease are found in a region called the substantia nigra, which controls movement, among other roles. "The neurons in this part of the brain are extremely active. Each one has over 300,000 connections and is continuously transmitting information," he said. "These neurons require good support in the form of their fat and cholesterol membrane. If the right types of fat aren't available, then cell integrity will be sub-par and they could be prone to damage."
Dr. Sack and his colleagues plan some early-stage clinical studies on the connection between fat metabolism and Parkinson's. They will continue working with the NIH Parkinson's Clinic and encourage patients to participate in the research as it moves forward.
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