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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.
Article
Alpha-synuclein overexpression can drive microbiome dysbiosis in mice
Growing evidence indicates that persons living with Parkinson’s disease (PD) have a unique composition of indigenous gut microbes. Here, the authors used a transgenic mouse strain, which overexpress wild-type human α-syn to test how the gut microbiome composition responds in this model of PD pathology during aging.
Article
Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease
Published: The authors explored the role of resident macrophages in alpha-synuclein-mediated neuroinflammation. They found that border-associated macrophages (BAMs) play a key role in alpha-synuclein induced neuroinflammation where BAMs play a role in immune cell recruitment, infiltration, and antigen presentation. View original preprint.
Teams
Article
Dopamine transporter and synaptic vesicle sorting defects initiate auxilin-linked Parkinson’s disease
Published: Auxilin helps in recycling of synaptic vesicles to facilitate neurotransmission and loss of auxilin is associated with PD. The authors show auxilin knockout mice exhibit typical PD pathology, dopamine transport is disrupted due to slower dopamine reuptake kinetics, and that macroautophagy and defective synaptic vesicle sorting contributes to dopamine dyshomeostasis. View original preprint.
Article
Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures
Published: 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. Slpha-synuclein responding T cell gene expression profiles were associated with dysregulation in multiple cellular pathways related to PD genes. View original preprint.
Teams
Article
Unaltered T cell responses to common antigens in individuals with Parkinson’s disease
Published: 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. View original preprint.
Teams
Article
Integrated multi-cohort analysis of the Parkinson’s disease gut metagenome
Preprint: Here, the fecal metagenomes of those living with PD compared to others in the household were profiled from 4 geographically-distinct sites across 3 continents. The question was whether there were any specific PD-associated signatures in gut microbiome that are either enriched or depleted in PD.
Article
Central and Peripheral Inflammation: Connecting the Immune Responses of Parkinson’s Disease
Review: Authors highlight the important work being done that implicates central and peripheral inflammation in playing a role in PD. They also discuss how these two distant inflammations appear related and how that may be mediated by autoantigenic responses to α-synuclein.
Teams
Article
Similarities and differences between nigral and enteric dopaminergic neurons unravel distinctive involvement in Parkinson’s disease
Review: In this comparative review, authors compare the Dopamine neurons in the enteric nervous system, substantia nigra pars compacta, and ventral tegemental area, to assess whether, independent of their location or function, it is sufficient for neurons to be dopaminergic to be selectively vulnerable during the progression of PD.
Teams
Article
Subcellular and regional localization of mRNA translation in midbrain dopamine neurons
Published: Midbrain dopaminergic neurons have broad dendritic and axonal arborizations, but local protein synthesis is not understood here. 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. View original preprint.
Teams
Article
Subcellular proteomics of dopamine neurons in the mouse brain
Published: 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. Interestingly, the authors found striatal dopaminergic neurons house most proteins. View original preprint.
Teams
Article
Neuronal presentation of antigen and its possible role in Parkinson’s disease
Review: Patients with Parkinson’s disease and other synucleinopathies often exhibit autoimmune features, including CD4+ and some CD8+ T lymphocytes that recognize epitopes derived from alpha-synuclein. This article reviews the literature on neuronal antigen presentation and its potential role in PD.
Teams
Article
Interactions of dopamine, iron, and alpha-synuclein linked to dopaminergic neuron vulnerability in Parkinson’s disease and Neurodegeneration with Brain Iron Accumulation disorders
Review: This review analyzes the involvement of disrupted dopamine, alpha-synuclein, and iron pathways in dopamine neuron physiology and function, and discusses how disrupted interplay of dopamine, alpha-synuclein, and iron pathways may synergize to promote pathology and drive the unique vulnerability to disease states.
Teams
Article
Gut microbiome-mediated regulation of neuroinflammation
Review: The intestinal microbiome influences neuroinflammatory disease in animal models, and recent studies have identified multiple pathways of communication between the gut and brain. As preclinical research findings and concepts are applied to humans, the potential impacts of the gut microbiome – brain axis on neuroinflammation represent exciting frontiers for further investigation.
Teams
Article
Peripheral neuronal activation shapes the microbiome and alters gut physiology
Published: The enteric nervous system shapes the intestinal environment and communicates with various brain organs, including the brain. The authors used recombinant adeno-associated viral (rAAV) vectors and chemogenetics to map and activate enteric neurons in mice with spatial and temporal resolution. View original preprint.