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Key player in Parkinson's disease triggered neuron loss pinpointed

Source : ANI
Last Updated: Sat, Oct 20, 2012 05:30 hrs

By reprogramming skin cells from Parkinson's patients with a known genetic mutation, researchers have identified the damage to neural stem cells as a powerful player in the disease.

The scientists from the Salk Institute for Biological Studies found that a common mutation to a gene that produce the enzyme LRRK2, which is responsible for both familial and sporadic cases of Parkinson's disease, deforms the membrane surrounding the nucleus of a neural stem cell.

Damaging the nuclear architecture leads to destruction of these powerful cells, as well as their decreased ability to spawn functional neurons, such as the ones that respond to dopamine.

The researchers checked their laboratory findings with brain samples from Parkinson's disease patients and found the same nuclear envelope impairment.

"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," Juan Carlos Izpisua Belmonte, lead researcher of the study, 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," Belmonte said.

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

For example, they were able to use targeted gene-editing technologies to correct the mutation in patient's nuclear stem cells. This genetic correction repaired the disorganization of the nuclear envelope, and improved overall survival and functioning of the neural stem cells.

They were also able to chemically inhibit damage to the nucleus, producing the same results seen with genetic correction.

"This opens the door for drug treatment of Parkinson's disease patients who have this genetic mutation," Belmonte said.

Belmonte added that the new finding may also help clinicians better diagnose this form of Parkinson's disease.

"Due to the striking appearance in patient samples, nuclear deformation parameters could add to the pool of diagnostic features for Parkinson's disease," he added.

The study has been published online in Nature. (ANI)



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