Mutations of Genes Responsible for Recycling Cell Waste May Increase Risk of Parkinson’s, Study Finds

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Mutations and Parkinson's

Mutations of genes responsible for breaking down and recycling cell waste products may promote Parkinson’s disease, a study shows.

Scientists have known for some time that deficiencies in these lysosomal storage genes cause Gaucher disease and other disorders.

The study, “Excessive burden of lysosomal storage disorder gene variants in Parkinson’s disease,” was published in the journal Brain.

Lysosomes are cell components containing enzymes that degrade and recycle cell waste. If they fail to do their job, waste products accumulate in cells, triggering lysosomal storage disorders like Gaucher disease. One of the enzymes that lysosomes contain is beta glucocerebrosidase, or GBA.

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

“Individuals with Gaucher disease can have family members with Parkinson’s disease,” Robak added. “People who carry one defective copy of the GBA gene have a five- to eight-fold increase in the risk of having Parkinson’s disease later in life. In addition, another gene called SMPD1 [that is] related to lysosome storage disorders is emerging as a new risk factor for Parkinson’s disease.”

The Baylor team wanted to see whether mutations of 54 genes associated with lysosome storage disorders had links to Parkinson’s as well.

They discovered links between five genes and Parkinson’s — GBASMPD1CTSDSLC17A5 and ASAH1.

Fifty-six percent of the 1,156 Parkinson’s patients whose records they studied had at least one mutation of a lysosomal storage disorder gene. Up to 20 percent had more than one 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,” said Dr. Joshua Shulman, an assistant professor at Baylor College of Medicine who was a co-lead author of the study.

“It might be possible that Parkinson’s disease and lysosomal storage disorders have similar fundamental biological mechanisms,” added Shulman, who is also an investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital.

“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 concluded.

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