This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.
Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
Protocol
Collection of protocols of Team Deleidi used in the publication: “LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease”
Collection of protocols of Team Deleidi used in the publication: “LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease.”
Teams
Article
Mechanism of human PINK1 activation at the TOM complex in a reconstituted system
Preprint: The authors demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These molecular findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD.
Protocol
LRRK2 RCKW protein purification
Protein purification protocol for tag-less LRRK2RCKW as done by Leschziner and Reck-Peterson Labs. Same protocol can be used to purify LRRK1RCKW as well. Original protocol by David Snead. Modified by Yu Xuan Lin and Mariusz Matyszewski for publication.
Teams
Themes
Article
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074, and Thr1075) within the CORB GTPase domain
Leucine-rich-repeat-kinase 1 (LRRK1) and its homologue LRRK2 are multidomain kinases possessing a ROC-CORA-CORB containing GTPase domain and phosphorylate distinct Rab proteins. LRRK1 loss of function mutations cause the bone disorder osteosclerotic metaphyseal dysplasia, whereas LRRK2 missense mutations that enhance kinase activity cause PD. Here, the authors study the mechanism controlling LRRK1 activity and reveal a novel unexpected activation mechanism. View preprint.
Themes
Article
Response to: “Is Gauchian genotyping of GBA1 variants reliable?”
Preprint: To understand the cause of these discrepancies, the team reviewed their data, and concluded that they are misinterpreting Gauchian results in 8 of the 11 discrepant samples, and incorrectly using Gauchian to analyze low-coverage 1kGP samples.
Article
The annotation and function of the Parkinson’s and Gaucher disease-linked gene GBA1 has been concealed by its protein-coding pseudogene GBAP1
Here, the authors identify novel transcripts from both GBA1 and GBAP1, including protein-coding transcripts that are translated in vitro and detected in proteomic data, but that lack GCase activity.
Protocol
Rab8a expression and purification
Recombinant Rab8a expression and purification protocol as used by the Leschziner and Reck-Peterson Labs.
Teams
Themes
Protocol
LRRK1 expression and purification
Protein purification protocol for full-length LRRK1 as done by Leschziner and Reck-Peterson Labs.
Original protocol by Janice M. Reimer and Yu Xuan Lin.
Teams
Themes
Article
Structural Biology of LRRK2 and its Interaction with Microtubules
Review: This review focuses on new insights into the stucture of LRRK2’s cytosolic and microtubule-bound forms and challenges going forward.
Teams
Themes
Article
Structural basis for Parkinson’s Disease-linked LRRK2’s binding to microtubules
Preprint: LRRK2 mutations are a common cause of familial PD. In some circumstances, LRRK2 co-localizes with microtubules. The authors report a cryo-electron microscopy structure of the catalytic half of LRRK2, containing its kinase (closed conformation) and GTPase domains, bound to microtubules. Further, they identified amino acids that mediate microtubule binding.
Teams
Themes
Protocol
Preparation of LRRK2 RCKW cryo-EM grids
This is Leschziner’s Lab updated protocol for making cryo-EM grids for LRRK2 RCKW. This protocol, when using lower protein concentration, results in better monomer and dimer formation than the old protocol.
Teams
Themes
Article
A topographical atlas of αSyn dosage and cell-type expression in the mouse brain and periphery
Preprint: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and presents pathologically with Lewy pathology and dopaminergic neuron loss. This atlas provides much-needed insight into the cellular topography of αSyn, and provides a quantitative map to test assumptions about the role of αSyn in network vulnerability in PD and other αSynucleinopathies.
Protocol
GCaMP6f fluorescence in ex vivo intestinal preparation
Protocol for GCaMP6f imaging in ex vivo mouse intestinal tissue.
Code
Code for integrated multi-cohort analysis of the Parkinson’s disease gut metagenome
Detailed scripts to reproduce all analysis and data visualization for the paper, “Integrated multi-cohort analysis of the Parkinson’s disease gut metagenome,” including an interactive shiny R app for exploration of metagenomic features of interest in the data sets.