This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.
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
RASP: Optimal single fluorescent puncta detection in complex cellular backgrounds
Preprint: This sensitive, computationally efficient approach enables fluorescent puncta and cellular features to be distinguished in cellular and tissue environments with a sensitivity down to the level of the single protein.
Teams
Themes
Article
Protein aggregation and calcium dysregulation are the earliest hallmarks of synucleinopathy in human midbrain dopaminergic neurons
Preprint: Mutations in the SNCA gene causes PD and aggregates of alpha-synuclein are well known to be present in PD pathology. However, understanding the cellular sequence of events that occurs from mutation to pathology is unresolved. The authors find the temporal sequence of pathophysiological events that occur during neuronal differentiation that likely cause synucleopathies.
Teams
Themes
Article
Pseudogenes limit the identification of novel common transcripts generated by their parent genes
Preprint: Genetic analyses are often complicated by genomic sequences with high sequence similarity. Here, the authors examined the role of pseudogenes on transcriptomic analyses using GB1 and GBAP1 as examples.
Themes
Article
Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at 16q11.2 and MAPT H1 loci
These results enrich our understanding of physiological events regulating mitophagy and establish a novel pathway for drug targeting in neurodegeneration.
Themes
Article
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.
Themes
Article
Protein aggregation and calcium dysregulation are hallmarks of familial Parkinson’s disease in midbrain dopaminergic neurons
Our differentiation paradigm generates an efficient model for studying disease mechanisms in PD and highlights that protein misfolding to generate intraneuronal oligomers is one of the earliest critical events driving disease in human neurons, rather than a late-stage hallmark of the disease.
Teams
Themes
Article
ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2
Published: Parkinson’s disease likely reflects a complex interaction among genetic and environmental factors. Here, the role of nicotine, SV2 and the alpha-synuclein were examined. The study suggests that SV2 may be needed for the protection nicotine provides from Parkinson’s-related neurotoxicity. View original preprint.
Themes
Article
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). While PGBs have a detrimental effect on cognition, the underlying mechanism and clinical relevance of age-related PGB accumulation remain unknown. Here, the authors investigated the genetic basis and functional impact of age-related PGB accumulation in mice.
Teams
Themes
Article
The annotation and function of the Parkinson’s and Gaucher disease-linked gene GBA1 has been concealed by its protein-coding pseudogene GBAP1
Here, 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.
Article
Large-scale visualization of α-synuclein oligomers in Parkinson’s disease brain tissue
Parkinson’s disease is a neurodegenerative condition characterized by large intraneuronal aggregates in the brain. It has been hypothesized that these large aggregates may form from smaller soluble protein assemblies, often termed oligomers. ASA-PD, is a new imaging method to generate large-scale α-synuclein oligomer maps in post-mortem human brain tissue.
Teams
Themes
Article
Alpha-synuclein aggregates trigger anti-viral immune pathways and RNA editing in human astrocytes
Parkinson’s disease is a neurodegenerative disease characterized by a proteinopathy with marked astrogliosis. To investigate how a proteinopathy may induce a reactive astrocyte state, and the consequence of reactive astrocytic states on neurons, the authors generated hiPSC-derived astrocytes, neurons, and co-cultures and exposed them to small soluble alpha-synuclein aggregates.
Teams
Themes
Article
GLP-1 receptor agonism ameliorates Parkinson’s disease through 1 modulation of neuronal insulin signalling and glial suppression
Neuronal insulin resistance is linked to the pathogenesis of Parkinson’s disease through unclear, but potentially targetable, mechanisms. The authors delineated neuronal and glial mechanisms of insulin resistance and glucagon-like 1 peptide (GLP-1) receptor agonism in human iPSC models of synucleinopathy.
Teams
Themes
Article
Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity
Published: Using a single molecule FRET sensor, the authors track the intracelleular conformational states of alpha-synucelin and where these occur in the cell. The study suggests that oligomerization happens at the mitochonodria triggering neuronal toxicity. View original preprint.
Teams
Themes