APDA funded researcher published in Journal of Neuroscience – July 2016

APDA funded research demonstrates that alpha-synuclein inclusion formation in neurons can be blocked and that novel therapeutic compounds targeting this process by inhibiting LRRK2 kinase activity may slow progression of PD-associated pathology.

In 2013 and 2014, APDA awarded research grants to Laura Vopicelli-Daley, PhD, at the University of Alabama at Birmingham to fund her study on the impact of mutant LRRK2 on the spread of alpha-synuclein and help to determine a possible way of reducing or eliminating the threat of cell death in Parkinson’s disease (PD). The results of Dr. Volpicelli-Daley’s work were published in the July 13, 2016 issue of Journal of Neuroscience

This work is really important because it ‘connects the dots’ between two important factors in the cause of PD: alpha-synuclein, which is found aggregated in all cases of PD; and LRRK2, the most common genetic cause of the disease,” said David G. Standaert, MD, PhD, John N. Whitaker Professor, Chair of Neurology and Director, Division of Movement Disorders at the University of Alabama at Birmingham and Chairman of the APDA Scientific Advisory Board. “These results are certain to accelerate work on drugs to block LRRK2 which may be a means of slowing or stopping the progression of the disease.”

Alpha-Synuclein inclusions are found in the brains of patients with many different neurodegenerative diseases. It is know that mutation, duplication, or triplication of the alpha-synuclein gene can all cause PD. The G2019S mutation in LRRK2 is the most common known genetic cause of PD. The interaction between G2019S-LRRK2 and alpha-synuclein may uncover new mechanisms and targets for neuroprotection. Dr. Vopicelli-Daley, along with Dr. Andrew West, an expert on LRKK2 at UAB, showed that expression of G2019S-LRRK2 increases alpha-synuclein mobility and enhances aggregation of alpha-synuclein in primary cultured neurons and in dopaminergic neurons of the substantia nigra, a susceptible brain region in PD. Potent LRRK2 kinase inhibitors, which are being developed for clinical use, block the increased alpha-synuclein aggregation in G2019S-LRRK2-expressing neurons.

APDA is proud to continue to fund important research like this and to encourage the work of scientists who have devoted their careers to uncovering new treatments which may slow the progression of Parkinson’s disease and potentially lead to a cure.