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.
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Parkinson’s disease modeling in regenerative spiny mice (Acomys dimidiatus) captures key disease-relevant behavioral, histological, and molecular signatures
This paper models PD for the first time in a unique regenerative mammalian model, spiny mice, finding that 6-OHDA and αSyn PFFs induce robust pathology.
Faecalibacterium prausnitzii, depleted in the Parkinson’s disease microbiome, improves motor deficits in α-synuclein overexpressing mice
Treatment with an 8-member consortium of bacteria depleted in PD patients, or the single member F. prausnitzii, improves motor and GI function and reduces αSyn aggregates in the brain of a mouse model of PD.
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.
Serine-129 phosphorylation of α-synuclein is an activity-dependent trigger for physiologic protein-protein interactions and synaptic function
Phosphorylation of α-synuclein at the serine-129 site (α-syn Ser129P) is an established pathologic hallmark of synucleinopathies and a therapeutic target. In physiologic states, only a fraction of α-syn is phosphorylated at this site, and most…
Advances in AAV technology for delivering genetically encoded cargo to the nonhuman primate nervous system
Modern neuroscience approaches including optogenetics, calcium imaging, and other genetic manipulations have facilitated our ability to dissect specific circuits in rodent models to study their role in neurological disease. These approaches…
Peripheral neuronal activation shapes the microbiome and alters gut physiology
The authors specifically activate ChAT- or TH-expressing gut-associated neurons in mice and perform multi-omics, finding that subsets of peripherally-activated neurons differentially regulate the gut microbiome and host GI physiology.
Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain
Crossing the blood–brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few…
Synapsin E-domain is essential for α-synuclein function
Synucleins and synapsins are thought to cooperate to regulate synaptic vesicle recycling, but the mechanism is not known. Here we identify the synapsin E-domain as an essential binding partner of α-syn, enabling the function of α-syn at the…
α-Synuclein overexpression and the microbiome shape the gut and brain metabolome in mice
The authors quantitatively profiled nearly 630 metabolites in the gut, plasma and brain of α-synuclein-overexpressing mice with or without associated microbiota, finding tissue-specific changes driven by genotype, microbiome, and their interaction.
Spatial genomics of AAVs reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo
The authors identify widespread transcriptional crosstalk between enhancers and promoters delivered in different AAV vectors. They show that this arises from concatemerization and harness it to deliver large cargo for cell type-specific gene editing.
The gut microbiome promotes mitochondrial respiration in the brain of a Parkinson’s disease mouse model
In this paper, the authors find that the gut microbiome increases mitochondrial respiration and oxidative stress in the brain, which enhances motor symptoms in a mouse model of PD.
Molecularly-guided spatial proteomics captures single-cell identity and heterogeneity of the nervous system
The authors use immunostaining-guided laser capture microdissection coupled with LC-MS to perform single-cell spatial proteomics of neuronal populations from the cortex and substantia nigra in the brain and the myenteric plexus in the periphery.
Specific cell states underlie complex tissue regeneration in spiny mice
This paper compares regenerative and fibrotic healing to identify injury-induced cell states associated with persistent cell cycle progression and complex tissue regeneration in mammals.
Genetically encoded self-assembling synuclein for tunable Parkinsonian pathology in vitro and in vivo
This paper describes the self-assembling synuclein (SAS) system, a genetically-encoded tool for inducing temporally-controllable, tunable PD pathology in a wide range of in vitro and in vitro models.
