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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Microbiome signature of Parkinson disease in healthy and genetically at-risk individuals
Parkinson's disease (PD) is disabling and costly. *GBA1* variants increase PD risk. Gut microbiome changes can predict PD progression and identify those at risk, suggesting potential for disease modification through nutrition.
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.
A molecular atlas of cell-type specific signatures in the parkinsonian striatum
Progressive dopamine loss in PD affects striatum cells differently. Transcriptomic analysis in mouse and human models reveals changes in neuronal and glial populations, highlighting resilient and vulnerable cell types for potential new treatments.
Activation of transposable elements is linked to a region- and cell-type-specific interferon response in Parkinson’s disease
Study explores transposable elements role in Parkinson's disease neuroinflammation. TE activation in specific brain regions correlates with innate immune responses, indicating potential involvement in chronic neuroinflammation and PD progression.
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.
Post-fibrillization nitration of alpha-synuclein abolishes its seeding activity and pathology formation in primary neurons and in vivo
Increasing evidence points to post-translational modifications (PTMs) as key regulators of alpha-synuclein (α-Syn) function in health and disease. However, whether these PTMs occur before or after α-Syn pathology formation and their role in…
The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines
The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in fibroblasts.
DOPA pheomelanin is increased in nigral neuromelanin of Parkinson’s disease
Neuromelanin in the substantia nigra may be a key factor contributing to dopaminergic neuron vulnerability in Parkinson’s disease. Here, the authors investigated the relative composition and specific roles of pheomelanin and eumelanin in PD.
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.
Targeting the GBA1 pathway to slow Parkinson disease: Insights into clinical aspects, pathogenic mechanisms and new therapeutic avenues
The GBA1 gene encodes the lysosomal enzyme glucocerebrosidase (GCase), which is involved in sphingolipid metabolism. Biallelic variants in GBA1 cause Gaucher disease (GD), a lysosomal storage disorder characterised by loss of GCase activity and…
L1 retrotransposons drive human neuronal transcriptome complexity and functional diversification
The genetic mechanisms underlying the expansion in size and complexity of the human brain remains poorly understood. L1 retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological…
LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease
Leucine-rich repeat kinase 2 (LRRK2) is a kinase involved in different cellular functions, including autophagy, endolysosomal pathways, and immune function. Mutations in LRRK2 cause autosomal-dominant forms of Parkinson’s disease (PD).…
The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1
The authors identify novel transcripts from both GBA1 and GBAP1, including protein-coding transcripts that are translated in vitro and detected in proteomic data, but that lack GCase activity.
