When telephone lines go down, or Internet connections are lost, our communities temporarily come to a halt. What if something similar were found to be happening in Parkinson's? This is the focus of Dr. Schmitz and her team at the PDF Research Center at Columbia University Medical Center.
PDF Grant Programs
Are you interested in furthering Parkinson's science? View PDF's open grant programs.
LRRK2 phosphorylates novel tau epitopes and promotes tauopathy.
PDF's targeted PubMed search provides you with access to journal articles from the last 90 days that may be pertinent to Parkinson's disease research.
Not what you're looking for? Do you need informational publications about Parkinson's targeted for people living with Parkinson's, caregivers and family members? Please browse PDF's educational materials and programs - which are all available electronically or in print. Order for yourself, a loved one or in bulk for your patients or support group.
Acta Neuropathol 2013 Oct;
Authors: Rachel M Bailey, Jason P Covy, Heather L Melrose, Linda Rousseau, Ruth Watkinson, Joshua Knight, Sarah Miles, Matthew J Farrer, Dennis W Dickson, Benoit I Giasson, Jada Lewis
Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.
Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of familial Parkinson's disease (PD). The neuropathology of LRRK2-related PD is heterogeneous and can include aberrant tau phosphorylation or neurofibrillary tau pathology. Recently, LRRK2 has been shown to phosphorylate tau in vitro; however, the major epitopes phosphorylated by LRRK2 and the physiological or pathogenic consequences of these modifications in vivo are unknown. Using mass spectrometry, we identified multiple sites on recombinant tau that are phosphorylated by LRRK2 in vitro, including pT149 and pT153, which are phospho-epitopes that to date have been largely unexplored. Importantly, we demonstrate that expression of transgenic LRRK2 in a mouse model of tauopathy increased the aggregation of insoluble tau and its phosphorylation at T149, T153, T205, and S199/S202/T205 epitopes. These findings indicate that tau can be a LRRK2 substrate and that this interaction can enhance salient features of human disease.
PMID: 24113872 [PubMed - as supplied by publisher]