Output 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.
-
Output Type
-
Program
-
CRN Team Name
-
Theme
Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress
Cryo-ET showed protein aggregates, altered cristae, and reduced ribosome complexes in stressed mitochondria. Mitochondrial Hsp60 undergoes conformational changes to aid in protein folding, shedding light on mitochondrial proteostasis mechanisms.
Cortico-amygdala synaptic structural abnormalities produced by templated aggregation of α-synuclein
PD and DLB involve α-syn inclusions in the amygdala affecting cognition and emotions. Cortico-amygdala synapses with α-syn aggregates show increased volume of synapses, potentially contributing to behavioral impairments.
Single cell eQTL mapping reveals convergent glial–neuronal risk architecture in Parkinson’s disease
We identify 125 functional risk genes for 50 loci—nearly doubling supported genes—and assign genes and cell types to over half of GWAS signals. Unexpectedly, 51% of risk genes are regulated in glia, particularly oligodendrocytes and their…
A framework for efficient CRISPRi-mediated silencing of retrotransposons in human pluripotent stem cells
This methods paper outlines silencing transposable elements in hiPSCs using CRISPRi. Describes gRNA design, validation via multiome approach. Enables functional studies on TE transcription in hiPSC models.
Behavioral screening defines three molecular Parkinsonism subgroups in Drosophila
We created a new collection of 24 genetically well-controlled Drosophila models of familial forms of parkinsonism. Using unbiased behavioral screening and machine learning we identified three clusters of mutants that converge.
Integrating Long-Read Structural Variant Analysis with single-nucleus RNA-seq to Elucidate Gene Expression Effects in Disease
Long-read sequencing in PD brain samples identified 74,552 structural variants. Integrating RNA sequencing data revealed SVs near PD-related genes impacting cell type-specific expression, highlighting the importance of SVs in complex diseases.
Modeling cis-regulatory variation in human brain enhancers across a large Parkinson’s Disease cohort
GWAS have linked more than hundred non-coding genomic loci to Parkinson’s disease (PD) risk. Here, we establish a unique resource and new sequence modeling strategies to interpret functional non-coding variation in the human brain.
ATP13A2 Loss of Function-Driven Polyamine Dysregulation Induces SAM Depletion and Epigenetic Astrocyte Toxicity
Loss of ATP13A2 function leads to lysosomal polyamine sequestration, depleting cytosolic polyamines in astrocytes. This triggers compensatory polyamine biosynthesis, diverting SAM from DNA methylation and promoting neuroinflammation.
Dopamine release from Parkinson’s patient-derived neurons is disrupted due to impaired synaptic vesicle loading
Human Parkinson's patient neurons with SNCA-triplication mutation exhibit reduced dopamine release due deficits in dopamine loading and handling.
TEsingle enables locus-specific transposable element expression analysis at single-cell resolution
TEsingle is a tool for analyzing transposable elements (TE) and gene expression in single-cell data. The tool reveals cell-type specific TE expression in Parkinson's Disease patients' brain tissues.
Selective loss of Primary Cilia and Neurotrophic Signaling in G51D α-Synuclein Mice Highlights a Common Pathway to Parkinson’s Disease
G51D α-synuclein mice mimic disease symptoms, showing cilia loss in specific neurons and impaired neurotrophic signaling, contributing to disease progression. This highlights the role of ciliary dysfunction in Parkinson’s.
Cardiac-sympathetic state predicts action restraint, gated by demonstrated agency
In healthy humans, beat-to-beat cardiac contractility during incentivized reaching predicts action restraint. Cardiac-sympathetic outflow flexibly shapes speed–accuracy tradeoffs under reward and loss contexts, beyond simple action mobilization.
A RAB7A Phosphoswitch Coordinates Rubicon Homology Protein Regulation of PINK1/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.
Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders
Reelin levels might modulate the numbers of striatal interneurons and the density of the nigrostriatal dopaminergic projections, suggesting that these changes may be involved in the protection of Reelin against neuropsychiatric disorders.
Integrated multi-cohort analysis of the Parkinson’s disease gut metagenome
The authors perform metagenomic sequencing of multiple geographically-disparate cohorts and find that stereotypic changes in the functional metabolic potential of the gut microbiome are a consistent feature of PD.
