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LRRK2 Overactivation Linked to Parkinson Disease

Researchers show hyperactive LRRK2 mutations lead to shorter, unbranched neurites

WEDNESDAY, Nov. 22 (HealthDay News) -- Mutations in the LRRK2 gene reduce neurite length and branching, and may contribute to the development of Parkinson disease, according to in vitro and animal research published in the Nov. 22 issue of Neuron.

Because LRRK2 mutations have been previously linked to a familial form of Parkinson disease, Asa Abeliovich, M.D., Ph.D., of Columbia University Medical Center in New York City, and colleagues investigated its role in neuron morphology.

They showed that mutations causing overactivation of the LRRK2 gene product caused reduced branching and neurite length in both cultured neurons and in rat brain, while reducing LRRK2 expression caused just the opposite -- more branches and longer neurite length. The hyperactive mutations led to accumulation of Parkinson-associated inclusions and ultimately to neuron cell death.

The authors suggest that a LRRK2 mutation could be used to develop models of Parkinson disease in other animals including primates. "These cellular and animal models may promote the discovery of effective therapeutics for LRRK2-associated disease," they conclude.

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