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Neural stem cells pinpointed as "powerful players" in Parkinson's disease

The team, from the Salk Institute for Biological Studies, was led by Juan Carlos Izpisua Belmonte, Ph.D. They found that a common mutation to a gene that produces the enzyme LRRK2 deforms the membrane surrounding the nucleus of a neural stem cell. LRRK2 is responsible for both familial and sporadic cases of Parkinson's disease. Damaging the nuclear architecture leads to destruction of these powerful cells, as well as their decreased ability to spawn functional neurons.

The researchers checked their laboratory findings with brain samples from Parkinson's disease patients and found the same nuclear envelope impairment. Their study is reported Oct. 17 in the online issue of Nature.

"This discovery helps explain how Parkinson's disease, which has been traditionally associated with loss of neurons that produce dopamine and subsequent motor impairment, could lead to locomotor dysfunction and other common non-motor manifestations, such as depression and anxiety," Dr. Belmonte said.

"Similarly, current clinical trials explore the possibility of neural stem cell transplantation to compensate for dopamine deficits. Our work provides the platform for similar trials by using patient-specific corrected cells. It identifies degeneration of the nucleus as a previously unknown player in Parkinson's."

Although they don't yet know whether these nuclear aberrations cause Parkinson's disease or are a consequence of it, the researchers say the discovery could offer clues about potential new therapeutic approaches.

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Salk Institute for Biological Studies