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Parkinson Disease: Functional Assessment, Gene Disruptions, and More

New Parkinson disease studies offer insights into topics such as LRRK2 G2019S transgene activity, preclinical drug development, and neuroprotection in Parkinson disease.

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New Parkinson disease studies offer insights into topics such as LRRK2 G2019S transgene activity, preclinical drug development, neuroprotection in Parkinson disease, and more. Scoll through the slides for links to the studies.

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Modification to Pfeffer Questionnaire proposes 3.5 as cutoff point to define functional impairment in patients with Parkinson disease.[1] See: Modified Pfeffer Questionnaire for Functional Assessment in Parkinson Disease.

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Alpha-syn transgenic mouse models used to define potential efficacy and target engagement of novel disease-modifying candidate therapeutics.[2] See: Animal models of α-synucleinopathy for Parkinson disease drug development.

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Inhibition of LRRK2 kinase affects myeloid progenitors and myeloid cell differentiation. Abnormal LRRK2 activity can alter bone marrow myelopoieses, peripheral myeloid cell differentiation, and intestinal immune homeostasis.[3] See: Parkinson disease-associated LRRK2 G2019S transgene disrupts marrow myelopoisesis and peripheral Th17 response.

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Pathogenic mutations, particularly those in the LRRK2 GTPase and COR domains, increase LRRK2 kinase activities. Small molecule LRRK2 kinase inhibitors block these activities and provide neuroprotection.[4] See: Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease.

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References

1. Almeida KJ, deMacedo LP, Lemos de Melo Lobo Jofili Lopes J, et al. Modified Pfeffer Questionnnaire for Functional Assessment in Parkinson Disease. J Geriatr Psychiatry Neurol. January 2017; Epub ahead of print.

2. Koprich JB, Kalia LV, Brotchie JM. Animal models of a-synucleinopathy for Parkinson disease drug development. Nat Rev Neurosci. July 2017; Epub ahead of print.

3. Park J, LeeJW, Cooper SC, et al. Parkinson disease-associated LRRK2 G2019S transgene disrupts marrow myelopoisesis and peripheral Th17 response. J Leukoc Biol. July 2017; Epub ahead of print.

4. West AB. Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease. Exp Neurol. July 2017; Epub ahead of print.

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