Protein linked to Parkinsonís disease may regulate fat metabolism
Preliminary NIH study may have implications for early onset of the disease
National Institutes of Health researchers have found that Parkin, an important protein linked with some cases of early-onset Parkinsonís disease, regulates how cells in our bodies take up and process dietary fats.
Parkinsonís disease is a complex, progressive, and currently incurable neurological disorder characterized by shaking, stiffness, slowed movement, and impaired balance. Parkinsonís 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 Parkinsonís activist Michael J. Fox, is known as early-onset Parkinsonís.
Parkin mutations are present in as many as 37 percent of early-onset Parkinsonís cases. However, laboratory mice with defective Parkin do not display obvious signs of the disease. This preliminary study, which will appear online in the Journal of Clinical Investigation on Aug. 25, suggests defective Parkin may indirectly contribute to the development of some early-onset Parkinsonís by changing the amount and types of fat in peopleís bodies.
ďThis discovery shows that the clues to understand Parkinsonís disease may not necessarily be in the brain,Ē said study leader Michael Sack, M.D., chief of the Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes at the NIHís National Heart, Lung, and Blood Institute.
The research team, composed of scientists from the NHLBI and the NIHís 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 Parkinsonís 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 Parkinsonís, 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. ďThe neurons in this part of the brain are extremely active. Each one has over 300,000 connections and is continuously transmitting information,Ē he said. ďThese neurons require good support in the form of their fat and cholesterol membrane. If the right types of fat arenít available, then cell integrity will be sub-par and they could be prone to damage.Ē
Dr. Sack and his colleagues plan some early-stage clinical studies on the connection between fat metabolism and Parkinsonís. They will continue working with the NIH Parkinsonís Clinic and encourage patients to participate in the research as it moves forward.
To schedule an interview with Dr. Sack or learn more about the study, contact the NHLBI Office of Communications at 301-496-4236 or NHLBI_news@nhlbi.nih.gov.
The National Heart, Lung, and Blood Institute (NHLBI) is a component of the National Institutes of Health. NHLBI plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at: www.nhlbi.nih.gov.
NINDS (www.ninds.nih.gov) is the nationís leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease ó a burden borne by every age group, by every segment of society, by people all over the world.
About the National Institutes of Health (NIH): NIH, the nationís medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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