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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.
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 bioprinting of human neural tissues with functional connectivity
Probing how human neural networks operate is hindered by the lack of reliable human neural tissues amenable to the dynamic functional assessment of neural circuits. Team Scherzer developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter.
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3D imaging of neuronal inclusions and protein aggregates in human neurodegeneration by multiscale X-ray phase-contrast tomography
Preprint: This study leverages X-ray phase-contrast tomography for detailed analysis of neurodegenerative diseases focusing on the 3D visualization and quantification of neuropathological features within fixed human postmortem tissue.
A comparative analysis of Parkinson’s disease and inflammatory bowel disease gut microbiomes highlights shared depletions in key butyrate-producing bacteria
To identify shared and distinct features of the PD and IBD microbiome, the authors performed a joint analysis of 54 PD, 26 IBD, and 16 healthy control gut metagenomes recruited from clinics at the University of Florida and directly compared the gut microbiomes from PD and IBD persons.
Teams
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.
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A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy
Published: 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. View original preprint.
Teams
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.
Teams
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.
Teams
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.
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A neurocomputational view of the effects of Parkinson’s disease on speech production
This article reviews the role of cortico-basal ganglia circuits in speech motor learning and execution in Parkinson’s disease.
Teams
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.
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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.
Teams
A proteome-wide quantitative platform for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs
Using a library of membrane-active polymers the authors have developed a platform for the high-throughput analysis of the membrane proteome. The platform enables near-complete spatially resolved extraction of target membrane proteins directly from their endogenous membranes into native nanodiscs that maintain the local membrane context.
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A RAB7A phosphoswitch coordinates Rubicon Homology protein regulation of Parkin-dependent mitophagy
Published: 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. View original preprint.
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