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.
Available ASAP-related hPSC collection from Team Studer
Collection of human pluripotent stem cell lines from Team Studer consisting of isogenic GBA, LRRK2, SNCA series across three genetic backgrounds, KI-reporter lines for TOMM20 for mitochondria, b-actin for cytoskeleton, LAMB1 for cell membrane and LAMP1 for lysosomes, a-synuclein overexpression lines for Lewy body-like aggregation models, and other hPSC resources.
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The Parkinson’s disease protein alpha-synuclein is a modulator of Processing-bodies and mRNA stability
Publication: The paper describes a new function for alpha synuclein – an ability to bind to structures known as a “P-body”. P-body machinery in the cell regulates the expression of our genes through mRNAs. When alpha-synuclein abnormally accumulates, the physiologic structure and functions of the P-body are lost.
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Induced pluripotent stem cells: a tool for modeling Parkinson’s disease
Review: Recent advances in induced pluripotent stem cell (iPSC) technology have made it possible to generate patient-derived DA neuronal cell culture and organoid models of PD. These models have contributed to understanding disease mechanisms and the identification of novel targets and therapeutic candidates.
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Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions
Published: Intracellular inclusions accompanying neurodegeneration are histopathologically and ultrastructurally heterogeneous but the significance of this heterogeneity is unclear. iPSC models do not form inclusions in a reasonable timeframe and suffer from limited tractability. The authors developed an iPSC toolbox utilizing piggyBac-based or targeted transgenes to rapidly induce CNS cells with concomitant expression of aggregation-prone proteins. View original preprint.
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The Parkinson’s disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability
Genetic modulation of P-body components alters αS toxicity, and human genetic analysis lends support to the disease-relevance of these interactions. Beyond revealing an unexpected aspect of αS function and pathology, the authors’ data highlight the versatility of conformationally plastic proteins with high intrinsic disorder.
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Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies
Conventional genetic analyses are underpowered to address whether neurodegenerative diseases linked to misfolding of the same protein share genetic risk drivers or whether different protein-aggregation pathologies in neurodegeneration are mechanistically related. The authors study patients based on protein aggregation phenotype to detect variants in a targeted set of genes.
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Immune stimulation of human induced pluripotent stem cells (hiPSC)-derived glia with lipopolysaccharide (LPS)
The authors propose the use of LPS as a positive control for microglia activation assays (e.g., phagocytosis assay, cytokine production, and secretion), and as a phenotyping tool to investigate disease-mutated microglia by comparing to disease-relevant stimuli.
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SARS-CoV-2 infection causes dopaminergic neuron senescence
COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, the authors show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
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Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration
Aging is the biggest risk factor for the development of Alzheimer’s disease (AD). Here, the authors performed a whole-genome CRISPR screen to identify regulators of neuronal age and show that the neddylation pathway regulates both cellular age and AD neurodegeneration in a human stem cell model.
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Contextual AI models for single-cell protein biology
Here, the authors introduce PINNACLE, a geometric deep-learning approach that generates context-aware protein representations. PINNACLE’s ability to adjust its outputs on the basis of the context in which it operates paves the way for large-scale context-specific predictions in biology.
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Integrating population genetics, stem cell biology, and cellular genomics to study complex human diseases
Here, the authors discuss how the intersection of stem cell biology, population genetics, and cellular genomics can help resolve the functional consequences of human genetic variation.
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TNF-NF-κB-p53 axis restricts in vivo survival of hPSC-derived dopamine neurons
The authors identified p53-mediated apoptotic cell death as a major contributor to dopamine neuron loss and uncovered a causal link of TNFa-NFκB signaling in limiting cell survival.
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The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons
In this study, the authors utilized human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway.
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hPSC passaging and propagation on laminin521 V.1
hPSC Passaging and propagation using Laminin521 and EDTA. Laminin actively supports survival, prevents spontaneous differentiation, and increases plating efficiency, thus net expansion, and enables 100% confluent single cell layer epithelial monolayer culture. EDTA-based (Gentle Cell Dissociation Reagent) minimizes stress and enhances viability. Cell lines require little or no adaptation.
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