A field-wide challenge in Parkinson’s disease (PD) research is a general lack of availability for high-quality, reproducible, and readily accessible preclinical research tools. To address these challenges, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has developed a growing resource of preclinical tools for the PD research and drug development communities that endeavors to provide researchers with easy access to rigorously validated, research-enabling preclinical tools for molecular biology studies. An important aspect of MJFF’s preclinical tools portfolio are monoclonal antibodies that target PD-relevant proteins. In collaboration with academic experts and in partnership with Abcam and BioLegend, MJFF has sponsored the custom generation and independent validation of several monoclonal antibodies targeting both total and phosphorylated or modified versions of PD-relevant proteins including Parkin, PINK1, and LRRK2- and PINK1-related Rab proteins. Parkin and PINK1 (PTEN-induced putative kinase 1) are implicated in mitochondrial homeostasis pathways. Bi-allelic mutations in Parkin and PINK1 genes underlie young-onset, autosomal recessive PD. The Rab superfamily of proteins function generally in endocytosis, and a subset of Rab family members have been identified as key phosphorylation substrates of LRRK2 and PINK1 kinase activity, respectively. A select number of bona fide mutations in the gene LRRK2, which encodes the LRRK2 (leucine-rich repeat kinase 2) protein, are linked to late-onset, autosomal dominant PD, and these mutants increase LRRK2’s kinase activity. Herein we discuss the general MJFF antibody generation strategy and provide characterization data for ongoing custom antibody development projects, as well as antibody pipeline updates and commercial launch timelines for MJFF’s cumulative antibody collection. Ultimately, these MJFF-sponsored antibody projects aim to address field-wide challenges in the PD preclinical tools and reagents landscape and to overall accelerate Parkinson’s disease research.
Authors: Terina N. Martinez, Meng-Yun Chou, Dario R. Alessi, Paul Davies, Pawel Lis, Miratul Muqit, Michael G. Schlossmacher, Peggy Taylor, Brian O’Nuallain, Jacqueline Tokarew, Daniel El-Kodsi, Julianna Tomlinson, Shalini Padmanabhan, Marco Baptista, Nicole K. Polinski, Kuldip D. Dave