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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
Global ubiquitylation analysis of mitochondria in primary neurons identifies physiological Parkin targets following activation of PINK1
Published: Mutations in PINK1 and Parkin are implicated in PD via abherrant mitophagy. The authors identified ubiquitylated substrates of endogenous Parkin in mouse neurons by proteomic analysis. They identified and validated 22 protein targets of Parkin that are conserved in human neurons providing a functional Parkin landscape in neuronal cells. View original preprint.
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Article
Global ubiquitylation analysis of mitochondria in primary neurons identifies endogenous Parkin targets following activation of PINK1
Published: Loss-of-function mutations in Parkin cause disruption of mitophagy and are associated with PD. Yet, much of the biology surrounding Parkin function has taken place in artificial cell systems. The authors used human neurons to identify and validate 22 protein targets of Parkin, providing a functional Parkin landscape in neuronal cells.
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Article
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain
Preprint: This study describes how PKC isoforms are able to phosphorylate LRRK1 at 3 sites in a key regulatory domain of the protein (GTPase domain) inducing LRRK1’s kinase activity. Interestingly, this is not seen with the PD-associated LRRK2, suggesting that PKC isoforms do not regulate LRRK2.
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Article
Impact of 100 LRRK2 variants linked to Parkinson’s Disease on kinase activity and microtubule binding
Published: LRRK2 is a promising candidate for PD therapeutics via reduction of its kinase activity. The authors investigated 98 LRRK2 variants and their effects on function. They found 22 variants that robustly stimulated LRRK2 kinase activity and 12 variants that suppressed microtubule association in the presence of Type 1 kinase inhibitors. View original preprint.
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Article
Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain
Published: Pathogenic mutations in LRRK2 are known to cause loss of primary cilia in neurons. The authors show that cilia loss is seen very early in mice harboring the most common LRRK2 mutation. Further, they show that this loss of cilia in astrocytes disrupted signaling pathways required for dopamine neuron maintenance. View original preprint.
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Protocol
Introducing GolgiTag to Cells and Immunoprecipitation of Golgi
A protocol for rapidly purifying Golgi across various cell lines and tissues without any modification. The Golgi purified using this method are highly enriched, intact, contaminant-free and, depending on solubilisation buffer, could be used for various downstream applications, such as proteomics and metabolomics.
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Protocol
Reconstitution of LRRK2 membrane recruitment onto planar lipid bilayers
A method to monitor the recruitment of purified LRRK2 kinase onto planar lipid bilayers containing lipid-anchored Rab10 protein using Total Internal Reflection Fluorescence (TIRF) Microscopy.
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Article
Isotope tracing for investigating Parkinson’s metabolism, neuro-metabolism and beyond
Review: Here, authors review recent work utilizing metabolic tracing to study health and disease, and highlight its application to interrogate subcellular, intercellular, and in vivo metabolism. They also discuss the current challenges and opportunities to expand the utility of isotope tracing to new research areas.
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Article
PINK1 and Parkin: unlocking a mitochondrial quality control pathway linked to Parkinson’s disease
Review: This review focuses on understanding the PINK1/Parkin-mediated mitochondrial quality control pathway through the lens of abherrant immune activation as a driver of dopaminerigic neuron loss following the loss of PINK and Parkin.
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Article
Structural basis for the specificity of PPM1H phosphatase for Rab GTPases
Published: LRRK2 acts by adding a phosphate group to enzymes known as Rab GTPases, which causes new biological events. The authors analyzed the structure of an enzyme, PPM1H, that counteracts LRRK2 by removing the phosphate group it adds to Rab GTPases. View original preprint.
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