Nav: Home

Defects in cell's 'waste disposal system' linked to Parkinson's

November 14, 2017

An international study has shed new light on the genetic factors associated with Parkinson's disease, pointing at a group of lysosomal storage disorder genes as potential major contributors to the onset and progression of this common neurodegenerative disorder. The study appears in the journal Brain.

"In recent years, defects in the glucocerebrosidase (GBA) gene have been identified as significant risk factors for Parkinson's disease. Deficiencies in this gene also are known to cause Gaucher disease, a lysosomal storage disorder," said first author Dr. Laurie Robak, instructor of molecular and human genetics at Baylor College of Medicine.

The lysosomes are sac-shaped structures inside all cells that are in charge of clearing the waste produced by the cells. The sacs contain enzymes that degrade cellular waste into its constituent components, which the cell can recycle or discard. When lysosomes fail and cellular waste accumulates, disease follows. Gaucher disease is one of about 50 lysosomal storage disorders.

"Individuals with Gaucher disease can have family members with Parkinson's disease," Robak said. "People who carry one defective copy of the GBA gene have a 5- to 8-fold increase in the risk of having Parkinson's disease later in life. In addition, another gene called SMPD1 related to lysosome storage disorders is emerging as a new risk factor for Parkinson's disease."

In this study, the researchers investigated whether changes in lysosome storage disorder genes in general could be linked to risk for Parkinson's disease. They compiled a list of 54 genes involved in lysosome storage disorders and determined whether a population with Parkinson's disease was enriched for defective forms of these genes.

Genetics links pediatric condition to risk for a disease that usually affects adults

Lysosomal storage disorders are predominantly diagnosed in children. Thanks to the combined expertise of adult neurologists specializing in Parkinson's disease and both pediatricians and geneticists focusing on childhood lysosomal disorders, the research team was able to make a connection between childhood conditions and the risk for Parkinson's disease later in life.

"We studied the largest Parkinson's disease genetic dataset currently available and found that, although each of the damaging mutations within these genes is individually uncommon, they are common as a group within the Parkinson's cohort," said corresponding authors Dr. Joshua Shulman, assistant professor of neurology, neuroscience and molecular and human genetics at Baylor College of Medicine and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital.

The researchers found at least one of the damaging mutations in more than half of the cohort. Twenty percent carry more than one damaging mutation.

"Although more research remains to be done, these data suggest the interesting possibility that damage to the lysosome might be at the core of Parkinson's disease," Shulman said. "It might be possible that Parkinson's disease and lysosomal storage disorders have similar fundamental biological mechanisms."

"Better understanding the genetics of Parkinson's disease is important because it can lead to improved diagnosis, more insights on how the disease develops and progresses and perhaps suggest new therapies," Robak said.
-end-
Other contributors to this work include Iris E. Jansen, Jeroen van Rooij, André G. Uitterlinden, Robert Kraaij, Joseph Jankovic, the International Parkinson's Disease Genomics Consortium and Peter Heutink. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Jan and Dan Duncan Neurologic Research Institute, Texas Children's Hospital, German Center for Neurodegenerative Diseases, VU University Medical Center, Erasmus MC and Netherlands Consortium for Healthy Ageing. For a complete list of financial support sources, see the publication.

Baylor College of Medicine

Related Genetics Articles:

Improve evolution education by teaching genetics first
Evolution is a difficult concept for many students at all levels, however, a study publishing on May 23 in the open access journal PLOS Biology has demonstrated a simple cost-free way to significantly improve students' understanding of evolution at the secondary level: teach genetics before you teach them evolution.
Study unravels the genetics of childhood 'overgrowth'
Researchers have undertaken the world's largest genetic study of childhood overgrowth syndromes -- providing new insights into their causes, and new recommendations for genetic testing.
Could genetics influence what we like to eat?
Gene variants could affect food preferences in healthy people, according to a new study.
Reverse genetics for rotavirus
Osaka University scientists generate a new plasmid-based reverse genetics system for rotaviruses.
The genetics behind being Not Like Daddy
A common strategy to create high-yielding plants is hybrid breeding.
Understanding the genetics of human height
A large-scale international study involving more than 300 researchers, published today in Nature, heralds the discovery of 83 genetic variations controlling human height.
Animal genetics: The bovine heritage of the yak
Though placid enough to be managed by humans, yaks are robust enough to survive at 4,000 meters altitude.
New genetics clues into motor neuron disease
Researchers at the University of Queensland have contributed to the discovery of three new genes which increase the risk of motor neuron disease, opening the door for targeted treatments.
Your best diet might depend on your genetics
If you've ever seen a friend have good results from a diet but then not been able to match those results yourself, you may not be surprised by new findings in mice that show that diet response is highly individualized.
Using precision-genetics in pigs to beat cancer
Because of their similarities to people, using new technology in pigs turn up as a valuable alternative to rodent models of cancer.

Related Genetics Reading:

The Gene: An Intimate History
by Siddhartha Mukherjee (Author)

Genetics: A Conceptual Approach, 5th Edition
by Benjamin A. Pierce (Author)

Genetics: A Conceptual Approach
by Benjamin A. Pierce (Author)

Genetics: From Genes to Genomes, 5th edition
by Leland H. Hartwell (Author), Michael L. Goldberg (Author), Janice A. Fischer (Author), Leroy Hood (Author), Charles F. Aquadro (Author)

Genetics: Genes, genomes, and evolution
by Rachel Dawes Hoang (author), Iruka N. Okeke (author), Katherine Heston (author) Philip Meneely (author) (Author)

The Family Tree Guide to DNA Testing and Genetic Genealogy
by Blaine T. Bettinger (Author)

Genetics: Analysis and Principles
by Robert J. Brooker Professor Dr. (Author)

Genetics For Dummies
by Tara Rodden Robinson (Author)

Thompson & Thompson Genetics in Medicine (Thompson and Thompson Genetics in Medicine)
by Robert L. Nussbaum MD FACP FACMG (Author), Roderick R. McInnes CM MD PhD FRS(C) FCAHS FCCMG (Author), Huntington F Willard PhD (Author)

The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance
by Nessa Carey (Author)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Circular
We're told if the economy is growing, and if we keep producing, that's a good thing. But at what cost? This hour, TED speakers explore circular systems that regenerate and re-use what we already have. Guests include economist Kate Raworth, environmental activist Tristram Stuart, landscape architect Kate Orff, entrepreneur David Katz, and graphic designer Jessi Arrington.
Now Playing: Science for the People

#503 Postpartum Blues (Rebroadcast)
When a woman gives birth, it seems like everyone wants to know how the baby is doing. What does it weigh? Is it breathing right? Did it cry? But it turns out that, in the United States, we're not doing to great at asking how the mom, who just pushed something the size of a pot roast out of something the size of a Cheerio, is doing. This week we talk to anthropologist Kate Clancy about her postpartum experience and how it is becoming distressingly common, and we speak with Julie Wiebe about prolapse, what it is and how it's...