Defective cellular waste removal explains why Gaucher patients often develop Parkinson's disease

Astrocytes from GD mice are labeled with a mitochondrial specific dye (red/orange). The mitochondria in GD cells are small and fragmented compared to the filamentous structures in the WT cells. Nuclei are stained blue and are 10microns in diameter. Credit: Cell Metabolism, Osellame et al.:

Gaucher disease causes debilitating and sometimes fatal neurodegeneration in early childhood. Recent studies have uncovered a link between the mutations responsible for Gaucher disease and an increased risk of developing Parkinson's disease later in life. New research published online on May 23 in the Cell Press journal Cell Metabolism indicates that the neurodegeneration found in Gaucher disease stems from defects in processes that break down and remove unwanted material from cells. This defective trash removal in cells can lead to the toxic build-up of proteins found to be responsible for neurodegeneration in Parkinson's disease, providing insight into the link between the two diseases.

Investigators found that in Gaucher disease, defects in the cell's trash removal processes lead to a build-up of dysfunctional mitochondria, the energy-producing components of cells. Without an effective source of energy, neurons cannot function normally and eventually die. The failure to remove unwanted cellular material also causes the build-up of a protein called , which accumulates in a toxic form in the brain's of patients with Parkinson's disease. "The findings may help to explain the increased risk of Parkinson's disease amongst people carrying Gaucher's ," says senior author Dr. Michael Duchen of University College London in the United Kingdom.

Neurons from GD mice are labeled with a mitochondrial specific dye (red/orange). The mitochondria in GD cells are small and fragmented compared to the filamentous structures in the WT cells. Nuclei are stained blue and are 10microns in diameter. Credit: Cell Metabolism, Osellame et al.

Dr. Duchen and his colleagues made their discoveries by studying the properties of neurons in a mouse model of severe neuropathic Gaucher disease. "Our data show that routine clearance of dysfunctional mitochondria is a critical aspect of normal cell health, and the failure of this pathway initiates a destructive cycle that culminates in the accumulation of damaged mitochondria," says Dr. Duchen. The researchers suggest that these damaged mitochondria generate increased amounts of instigating a domino effect that causes further damage to the remaining mitochondria.

Neurons from WT mouse are labeled with a mitochondrial specific dye (red/orange). The mitochondria in GD cells are small and fragmented compared to the filamentous structures in the WT cells. Nuclei are stained blue and are 10microns in diameter. Credit: Cell Metabolism, Osellame et al.

The findings suggest that treatment strategies that target the trash removal and mitochondrial functions of cells might be developed to benefit patients with Gaucher and Parkinson's diseases.

More information: Cell Metabolism, Osellame et al.: "Mitochondria and quality control defects in a mouse model of Gaucher disease - links to Parkinson's Disease." dx.doi.org/10.1016/j.cmet.2013.04.014

Related Stories

Unleashing the watchdog protein

May 09, 2013

McGill University researchers have unlocked a new door to developing drugs to slow the progression of Parkinson's disease. Collaborating teams led by Dr. Edward A. Fon at the Montreal Neurological Institute and Hospital -The ...

Missing link in Parkinson's disease found

Apr 25, 2013

Researchers at Washington University School of Medicine in St. Louis have described a missing link in understanding how damage to the body's cellular power plants leads to Parkinson's disease and, perhaps ...

Recommended for you

Mechanism of Parkinson's spread demonstrated

19 hours ago

An international, interdisciplinary group of researchers led by Gabor G. Kovacs from the Clinical Institute of Neurology at the MedUni Vienna has demonstrated, through the use of a new antibody, how Parkinson's ...

Researchers debunk myth about Parkinson's disease

Sep 16, 2014

Using advanced computer models, neuroscience researchers at the University of Copenhagen have gained new knowledge about the complex processes that cause Parkinson's disease. The findings have recently been ...

User comments