Defects in cell’s ‘waste disposal system’ linked to Parkinson’s


November 14, 2017


Baylor College of Medicine


points at a group of lysosomal storage disorder genes as potential major
contributors to the onset and progression of Parkinson’s disease.


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

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.”

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.

Story Source:

Materials provided by Baylor College of Medicine. Note: Content may be edited
for style and length.


Journal Reference:

1.    Laurie A Robak et al. Excessive
burden of lysosomal storage disorder gene variants in Parkinson’s disease
. Brain,
2017 DOI: 10.1093/brain/awx285