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Platt_parkinson
Images: (left) Schematic: Do different levels of glucocerebrosidase (GCase) activity or its lipid substrates glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) cause different diseases? (right) Glucosylceramide levels in whole brain homogenates of FVB wildtype mice increase with normal aging, reminiscent of Parkinson’s disease.

A collaborative team of researchers from the Platt lab and the Isacson lab (McLean Hospital, Harvard Medical School) has found that elevated levels of certain types of lipids (fat molecules) in the brain, called glycosphingolipids, may be an early sign of Parkinson's disease.

Parkinson's disease is a degenerative, progressive disorder characterized by the loss of dopaminergic neurons, which are involved in movement performance. Aging is the highest risk factor for developing several neurodegenerative diseases, including Parkinson's disease.

Recently, researchers have been studying an interesting relationship between the risk of developing Parkinson’s disease and a group of disorders called lysosomal storage disorders, particularly Gaucher disease. Gaucher’s disease is caused by mutations that lead to loss of function in the glucocerebrosidase (GBA) gene.

Since aging is the most significant risk factor for developing Parkinson’s disease, DPhil student Mylene Huebecker from the Platt lab measured the levels of glycosphingolipids in the aging mouse brain, using young and old mice between 1.5 and 24 months of age. She found that the same glycosphingolipids, which are increased in the brains of Parkinson's disease patients, are also elevated in the brains of aged mice. Furthermore, the activity of the glucocerebrosidase enzyme, encoded by the gene GBA, was diminished with normal aging. These findings show that both genetics (GBA gene mutation) and aging can cause the same lipid elevations and enzymatic changes in the brain that are found in Parkinson's disease pathology. This study also helps to explain why patients with Gaucher’s disease have an increased risk for Parkinson’s disease and suggests that targeting lipid accumulation may slow down Parkinson’s progression.

 The paper has been picked up in several news/media sites around the world.