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.

Article

“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.

Article

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.

 

Article

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.

Article

A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy

Preprint: Cortical axons in conduits are severed by a media jet; then, brain-derived neurotrophic factor and striatal neurons in distal chambers promote axon regeneration. As additional conduits and chambers are easily added, this opens up the possibility of mimicking complex neuronal networks and screening drugs for their effects on connectivity.

Article

A leaky gut dysregulates gene networks in the brain associated with immune activation, oxidative stress, and myelination in a mouse model of colitis

Preprint: The team provides a comprehensive evaluation of multiple systems in a prevalent experimental model of intestinal permeability, which will inform future studies using this model and others, assist in the identification of druggable targets in the gut-brain axis, and contribute to our understanding of the concomitance of intestinal and neuropsychiatric dysfunction.

Article

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.

Article

A mono- and intralink filter (mi-filter) to reduce false identifications in cross-linking mass spectrometry data

The authors show that this simple and intuitive filter has a dramatic effect on different types of cross-linking data ranging from individual protein complexes over medium-complexity affinity enrichments to proteome-wide cell lysates and significantly reduces the number of false-positive identifications for inter-protein links in all these types of XL-MS data.

Article

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.

Article

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.

 

Article

A RAB7A phosphoswitch coordinates rubicon homology protein regulation of PINK1/Parkin-dependent mitophagy

Preprint: Structural and functional data support a model in which the TBK1-dependent phosphorylation of RAB7A serves as a switch, promoting mitophagy by relieving Rubicon inhibition and favoring Pacer activation.

Article

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.

Article

A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes

Preprint: These results define a pathway that integrates multiple stimuli at lysosomes to control the kinase activity of LRRK2. Aberrant activation this pathway may be of relevance in both Parkinson’s and Crohn’s diseases.

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.

Article

A unifying model for the role of the ATG8 system in autophagy

Review: The core ATG8 system is one of the most-studied autophagy components. Here, authors reconcile prior observations of the core ATG8 system into a unifying model. Bypass pathways of autophagy that function independently of the core ATG8 system are also discussed.