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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A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex
A data-driven molecular map of the DLPFC reveals distinct spatial domains and cell populations, offering insights into neuropsychiatric disorders. The study provides a roadmap for implementing spatial clustering approaches in the human brain.
Protein aggregation and calcium dysregulation are hallmarks of familial Parkinson’s disease in midbrain dopaminergic neurons
Mutations in SNCA gene cause PD by forming α-synuclein aggregates. Using hiPSCs, we traced pathophysiological events, revealing early oligomeric aggregate formation, calcium signaling impairments, and multiple cellular stresses leading to cell…
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.
ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2
The authors present ggtranscript, an R package that provides a fast and flexible method to visualize and compare transcripts from long-read sequences. This tool is an extension of ggplot2.
Splicing accuracy varies across human introns, tissues and age
This in-depth characterization of mis-splicing can have important implications for our understanding of the role of splicing inaccuracies in human disease and the interpretation of long-read RNA-sequencing data.
Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases
Genetic correlation between neurodegenerative and neuropsychiatric diseases was explored using local rg analysis. Unique relationships were found, suggesting shared genetic mechanisms and potential therapeutic targets in complex diseases.
Genome-wide determinants of mortality and motor progression in Parkinson’s disease
The authors examined the impact of gene variants on mortality and cognitive impairment in PD. Only the non-Gaucher disease causing GBA PD risk variant E326K, of the known PD risk variants, was associated with progression in PD.
Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at 16q11.2 and MAPT H1 loci
Impaired mitophagy is linked to familial PD. New study identifies KAT8 and KANSL1 as regulators of PINK1-dependent mitophagy, suggesting their role in idiopathic Parkinson’s. KANSL1 may be crucial in the disease, offering potential drug targets.
Structural conversion of α-synuclein at the mitochondria induces neuronal toxicity
Our study highlights intracellular conformational changes as a mechanism of de novo α-Syn oligomerization at mitochondrial membranes and subsequent neuronal toxicity, also observed in iPSC-derived neurons with A53T mutations from patients with PD.
Diabetes and neuroaxonal damage in Parkinson’s disease
Our findings affirm Uyar et al's report of an association between PD-DM and more severe neuroaxonal damage. T2DM and PD share several pathological processes, in par mediated by hyperglycemia and possibly diabetic neuropathy.
POLCAM: Instant molecular orientation microscopy for the life sciences
POLCAM is a simplified single-molecule orientation localization microscopy method, using a polarization camera, enabling fast easy implementation on fluorescence microscopes. Here, we apply it to alpha-synuclein fibrils.
RASP: Optimal single fluorescent puncta detection in complex cellular backgrounds
RASP, a bioimaging-segmentation method, outperforms existing methods by removing false positives + detecting features across various spatial scales. RASP enables precise analysis of cellular and tissue environments, down to single protein levels.
Polyglucosan body density in the aged mouse hippocampus is controlled by a novel modifier locus on chromosome 1
Aging can be associated with the accumulation of polyglucosan bodies (PGBs).Here, the authors investigated the genetic basis and functional impact of age-related PGB accumulation in mice.
Large-scale visualisation of α-synuclein oligomers in Parkinson’s disease brain tissue
ASA-PD (Advanced Sensing of Aggregates - PD) is a new imaging method to map α-synuclein oligomers in human brain tissue, revealing specific early proteinopathy markers in PD patients. This may aid in understanding disease mechanisms.
Alpha-synuclein aggregates trigger anti-viral immune pathways and RNA editing in human astrocytes
PD involves proteinopathy and astrogliosis. Oligomeric alpha-synuclein induces astrocyte inflammation, leading to neuronal toxicity. ADAR1-mediated RNA editing plays a role in sustaining inflammatory states, potentially driving PD neuroinflammation.
