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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Output Type
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Program
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CRN Team Name
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Theme
TNF-NF-κB-p53 axis restricts in vivo survival of hPSC-derived dopamine neurons
The ASAP-related findings are the DA neuron purification strategy developed (CD49e-/CD184+) developed and validated in this manuscript, which is suitable for PD-iPSC based disease modeling and DA-neuron related CRISPR screens from our consortium.
Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions
The authors developed an iPSC toolbox utilizing piggyBac-based or targeted transgenes to rapidly induce CNS cells with concomitant expression of aggregation-prone proteins.
The Parkinson’s disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability
The paper describes the ability of alpha-synuclein to bind to P-bodies, machinery that regulates the expression of our genes through mRNAs. When alpha-synuclein abnormally accumulates, the physiologic structure and functions of the P-body are lost.
The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons
Study shows SATB1, MIR22HG, and GBA genes form a pathway in Parkinson's Disease. Dysregulation leads to GluCer accumulation, causing cellular senescence in dopaminergic neurons, potentially explaining neuroinflammation seen in PD and aging.
Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies
The authors study patients based on protein aggregation phenotype to detect variants in a targeted set of genes.
Contextual AI models for single-cell protein biology
This study describes PINNACLE a deep learning approach establish context dependent networks. PINNACLE is a key algorithm used in our ASAP project to provide cell type , age-or disease context to our experimental datasets.
Integrating population genetics, stem cell biology and cellular genomics to study complex human diseases
This review describes current state-of-the art of pooled "village-style" hPSC-based assays. This is a major topic for disease modeling including PD and for linking disease with genetic and/or environmental risk and part of our experimental ASAP work.
SARS-CoV-2 infection causes dopaminergic neuron senescence
The ASAP-supported aspect of this study involves the DA neuron senescence work, and experiments using ASAP lines (isogenic a-SYN triplication) to assess interaction of genetic vulnerability with viral-induced senescence as PD penetrance factor.
Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration.
We found that neddylation-inhibition triggers age-related features in PSC-derived neurons for modeling AD or PD. This strategy can induce late-onset phenotypes including degeneration when applied to DA neurons from PD- versus isogenic control PSCs.
Induced Pluripotent Stem Cells: A Tool for Modelling Parkinson’s Disease
PD involves loss of dopaminergic neurons in the substantia nigra. Patient-derived iPSC models aid in understanding the disease and identifying potential treatments. More research is needed on age-related aspects and gene-environment interactions.
Cholesterol-mediated Lysosomal Dysfunction in APOE4 Astrocytes Promotes α-Synuclein Pathology in Human Brain Tissue
Development of a 3D model mimicking human brain tissue to investigate neurodegenerative diseases. It found that APOE4 increases α-Synuclein aggregation, linking astrocytes, cholesterol, and protein inclusions, offering potential therapeutic…