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Study provides first link between two major Parkinson’s genes

.... The study... provides the first link between the most common genetic risk factor for Parkinson’s and the hallmark accumulation of a protein called alpha-synuclein within the brains of people with Parkinson’s.
... we’ve known for six years now that 10 to 12 per cent of people with Parkinson’s have a mutation in one copy of a gene called glucocerebrosidase, or GBA. However, until now we have not understood how these mutations contribute to the disease and how they fit with other pieces of the puzzle, such as the accumulation of alpha-synuclein in the brain...”


...Using a series of experimental laboratory models, Dr. Schlossmacher and his colleagues have now shown that the GBA mutations found in Parkinson’s patients prevent brain cells from efficiently breaking down and removing alpha-synuclein.

“While the GBA mutations don’t cause Parkinson’s disease on their own, they do significantly increase the risk of developing the disease,... “This could explain why people with GBA mutations frequently develop Parkinson’s symptoms four to five years earlier than those without them.”

“These findings... could significantly accelerate the development of new treatments for Parkinson’s,” he adds. “Several companies have developed or are actively working on drugs that target GBA for another disease called Gaucher disease, and our research suggests that these drugs could potentially be useful in Parkinson’s, and in a related disease called Lewy body dementia.”

http://www.exchangemagazine.com/morn...day/040413.htm

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http://onlinelibrary.wiley.com/doi/1...22400/abstract

"Our results demonstrate that GBA mutants promote SNCA accumulation in a dose- and time-dependent manner, thereby supporting a biochemical link between GBA mutation carrier status and increased synucleinopathy risk. In cell culture models, this gain-of-toxic function effect can be mitigated by rapamycin. Loss-in-GCase-activity did not immediately raise SNCA concentrations but first led to neuronal ubiquitinopathy and axonal spheroids, a phenotype shared with other lysosomal storage disorders. Ann Neurol 2011."

http://en.wikipedia.org/wiki/Mammali...t_of_rapamycin

(Rapamycin is an mTOR inhibitor)
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mTOR inhibitors as therapies: mTOR inhibitors, e.g. rapamycin, are already used to prevent transplant rejection. Epigallocatechin gallate (EGCG), caffeine, curcumin and resveratrol inhibit mTOR.[33]