Rare genetic disease offers a unique insight into Alzheimer’s disease

Investigators at Massachusetts General Hospital seem to have found the mechanism behind the link between the above mentioned rare genetic disorder, Gaucher disease, neurodegenerative disease and Parkinson’s. In a report to be published in the July 8 Issue of Cell and receiving early online release, which describe how disruption of the molecular pathway that causes Gaucher disease leads to neuronal toxic deposits of the protein alpha-synuclein found in Parkinson’s disease and related disorders. In addition, high levels inhibit further syn-track associated with Gaucher’s, causing even more syn-deposition, a result that indicates therapies targeting this path can be a new option for patients with Parkinson’s disease.In Gaucher disease, which occurs mainly in children, patients inherit two copies of the inactive gene encodes an enzyme called glucocerebrosidase , a molecule that breaks down fat called glucocerebroside . The lack of functional GCAS leads to an accumulation of GlcCer levels in cellular compartments called lysosomes, where the phones are usually digested waste. GlcCer accumulation in organs such as liver, spleen, bone marrow, and sometimes the brain causes the symptoms of Gaucher disease, which are usually treated with replacement therapy GCAS missing enzyme.

‘Our results suggest that this molecular pathway is not restricted to patients with Gaucher disease and their families, some of which may have symptoms of Parkinson’s disease, but also to patients with the common form of Parkinson’s or other synucleinopathies,’ says Dimitri Krainc, MD , Ph., MassGeneral Institute for Neurodegenerative Disease , author of the study. ‘It seems that the interaction between the syn-filing and form a path for Gaucher feedback loop that ultimately leads to self-propagation of the disease.’

USC has collaborated with scientists from Monash University in Australia and the Institute of Nuclear Sciences in Serbia in this study. The article is based on research that was funded by the National Institutes of Health and the CHDI Foundation, Inc.

‘We now propose that the glucocerebrosidase activities targeted therapies can help break the cycle of syn-accumulation and neurodegeneration,’ said Krainc, associate professor of neurology at Harvard Medical School. ‘We are convinced that this path does not apply to any potentially disease characterized by syn-accumulation and are now in partnership with industry to develop new therapies for Parkinson’s disease, improving the targeting of glucocerebrosidase to lysosomes.

We hope that these treatments can prevent or reduce the accumulation of syn-and neurodegeneration resulting from diseases such as Parkinson’s disease and dementia with Lewy bodies. ‘