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.
“LRRK2 phosphorylation of Rab GTPases in Parkinson’s disease”
Review: This paper highlights new findings related to LRRK2-mediated phosphorylation of Rab GTPases and their consequences.
17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes
Published: This paper examines the H1 haplotype of the MAPT 17q.21.31 locus to better understand its contribution to PD. The authors found three novel H1 sub-haplotype blocks across the 17q.21.31 locus that is associated with PD risk.
3D-correlative FIB-milling and Cryo-ET of Autophagic structures in Yeast Cells
This protocol describes how to plunge-freeze yeast on EM grids and how to target autophagic structures by combining cryo confocal fluorescence data to FIB-milling and tomogram acquisition.
A Blueprint for Training and Development in GP2
This blog written by Dr. Alastair Noyce and Dr. Sara Bandres-Ciga discusses GP2’s plan to train students and investigators and the new considerations as a result of the COVID-19 pandemic.
A combined cell and gene therapy approach for homotopic reconstruction of midbrain dopamine pathways using human pluripotent stem cells
These results demonstrate the remarkable capacity for achieving functional and anatomically precise reconstruction of long-distance circuitry in the adult brain by matching appropriate growth-factor signaling to grafting of specific cell types.
A feed-forward pathway drives LRRK2 kinase membrane recruitment and apparent activation
Published: Mutations in LRRK2 that cause PD activate its kinase activity. These activating mutations of LRRK2 phosphorylate Rab GTPases. The authors define two binding sites on LRRK2 that deliver it to the surfaces of specific intracellular membranes, and then retain it there after an initial phosphorylation event. View original preprint here.
A fluorescence-based in vitro scrambling assay for yeast MCP1 and human XK
Detailed procedure of purification, reconstitution, and scrambling assay for both MCP1 and XK.
A letter to the patient community from Randy Schekman, ASAP Scientific Director
This blog written by Dr. Randy Schekman and Benjamin Stecher describes the motivation and beginnings of the ASAP initiative. It also includes a letter written to the PD comunity by Dr. Schekman.
A Markov random field model-based approach for differentially expressed gene detection from single-cell RNA-seq data
The MARBLES, a Markov Random Field model-based approach for differentially expressed gene detection from scRNA-seq data can capture cell-type relationships and account for sample variation by modeling cell-type-specific pseudobulk data. The authors used simulation results to compare this approach to existing methods from two scRNA-seq datasets.
A possible role for VPS13-family proteins in bulk lipid transfer, membrane expansion, and organelle biogenesis.
Review: This review focuses on the structure and function of the VPS13 family of proteins and discusses the prevailing hypthoses in the field regarding its role in lipid transport.
A prebiotic diet modulates microglia response and motor deficits in α-synuclein overexpressing mice (Dataset)
These studies uncover a novel microglia-dependent interaction between diet and motor symptoms in mice, findings that may have implications for neuroinflammation and PD.
A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice
Publication: The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, although mechanisms of gut-brain interactions remain incompletely defined. Here, the authors investigated whether a fiber-rich diet influences microglial function in α-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. View original preprint.
A single-cell atlas of cell types, states, and other transcriptional patterns from nine regions of the adult mouse brain
We report 690K single-cell transcriptomes from nine different brain regions from adult mice (Frontal and Posterior Cortex, Hippocampus, Thalamus, Cerebellum, Striatum, Globus Pallidus externus/Nucleus Basalis, Entopeduncular / Subthalamic Nuclei, & Substantia Nigra / Ventral Tegmental Area).
A step forward for LRRK2 inhibitors in Parkinson’s disease
Review: A discussion on learnings from phase 1 clinical trial for kinase inhibitors targeting LRRK2 that can provide the foundations for moving towards testing the efficacy of LRRK2 kinase inhibition in Parkinson’s disease.