(RxWiki News) Doctors and researchers frequently discover new links between disease, but often figuring out how the two are tied together can prove trickier.
Massachusetts General Hospital investigators have discovered the mechanism behind the link between neurodegenerative disorder Parkinson's disease and a rare genetic condition called Gaucher's disease.
"Prospective parents with a history of Gaucher's disease should seek genetic counseling."
Parkinson's is a common disorder characterized by tremors, rigidity, shaking and slowness of movement. Gaucher's disease is inherited and primarily occurs in children. It is characterized by the lack of an enzyme called glucocerebrosidase. The lack of the enzyme causes harmful substances to build up in the liver, spleen, bones and bone marrow, which prevents cells and organs from working properly.
Researchers said the disruption of the molecular pathway that causes Gaucher's disease leads to the toxic neuronal deposits of the protein alpha-synuclein (α-syn) found in Parkinson's and related disorders.
The rising α-syn levels further inhibit the Gaucher's-associated pathway, leading to even more α-syn deposition, a discovery that indicates therapies targeting this pathway might be a new option for patients with Parkinson's disease.
Dr. Dimitri Krainc, M.D., PhD, of the MassGeneral Institute for Neurodegenerative Disease and the study's senior author said that it appears that interaction between α-syn deposition and the Gaucher's pathway forms a feedback loop that eventually leads to self-propagating disease.
The research team found that mutations reducing the expression of glucocerebrosidase lead to excess glucocerebroside lipid in cultured neurons. By interacting with α-syn, those glucocerebroside lipids induce accumulation of the protein.
Brain tissue samples from a mouse model of Gaucher's and from patients with either Gaucher's or Parkinson's-related disorders also showed evidence connecting reduced glucocerebrosidase expression with increased α-syn deposition in neurons.
In both the cultured cells and in the animal and human samples, α-syn deposits were also associated with neurodegeneration.
Previous studies had suggested a connection between Parkinson's and Gaucher's disease, but the mechanism had not yet been identified. The research was published in the journal Cell.