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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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.
A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice
What should Parkinson's Disease patients eat? This study shows that dietary fiber impacts gut microbes and immune cells in the brain of a mouse model of Parkinson's.
Subcellular and regional localization of mRNA translation in midbrain dopamine neurons
Using, highly sensitive ribosome-bound RNA sequencing and imaging to characterize the translatome, the authors uncovered local mRNA translation of dopamine synthesis, release, and reuptake machinery in dendrites, but not axons.
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.
Dopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease
Auxilin participates in the uncoating of clathrin-coated vesicles (CCVs), thereby facilitating synaptic vesicle (SV) regeneration at presynaptic sites. Auxilin (DNAJC6/PARK19) loss-of-function mutations cause early-onset Parkinson’s disease…
Central and Peripheral Inflammation: Connecting the Immune Responses of Parkinson’s Disease
Authors highlight the important work being done that implicates central and peripheral inflammation in playing a role in PD.
Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease
Border-associated macrophages (BAMs) are crucial in Parkinson's disease pathogenesis by initiating neuroinflammation, highlighting a potential target for therapeutic intervention.
Unaltered T cell responses to common antigens in individuals with Parkinson’s disease
T cells have been shown to be overactive in individuals with PD. The authors tested a wide variety of commonly encountered immune targets on PD and non-PD control derived T cells and observed no differences between their immune responses.
Interaction of an α-synuclein epitope with HLA-DRB1*15:01 triggers enteric features in mice reminiscent of prodromal Parkinson’s disease
Interaction of α-syn32-46 and HLA-DRB1*15:0 is critical for gut inflammation and CD4+ T cell-mediated loss of enteric neurons in humanized mice, suggesting potential mechanisms of prodromal enteric PD.
Conserved and cell type-specific transcriptional responses to IFN-γ in the ventral midbrain
Neurons present antigens when exposed to IFN-γ, leading to MHC-I expression. IFN-γ induces MHC-I in neurons, glia, and microglia, with glia showing a stronger response. Neuronal response to IFN-γ is dependent on IFNGR signaling.
Neuronal Presentation of Antigen and Its Possible Role in Parkinson’s Disease
Patients with Parkinson's disease and synucleinopathies show autoimmune features, with T cells recognizing alpha-synuclein. Studies explore T cell-mediated neuronal death in PD and other disorders.
Subcellular proteomics of dopamine neurons in the mouse brain
Understanding the proteome of dopamine neuron is difficult due to the complex cytoarchitecture of the neurons. The authors were able to map the somatodendritic and axonal proteomes of midbrain dopaminergic neurons.
Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures
Recent findings identified PD-associated autoimmune features. Using RNA sequencing, the authors found a broad gene expression profile in memory T cells and a specific PD-associated gene signature.
Alpha-synuclein overexpression can drive microbiome dysbiosis in mice
Persons with PD have a unique gut microbe composition. Studies on human and rodent microbiomes before and during the disease are lacking. α-syn overexpression in mice alters gut microbiome with age, potentially impacting disease progression.
