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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
Synaptic Location Is a Determinant of the Detrimental Effects of alpha-Synuclein Pathology to Glutamatergic Transmission in the Basolateral Amygdala
Publication: α-Synuclein in mouse brain is not ubiquitously expressed among glutamatergic axon terminals in the basolateral amygdala (BLA). This work looks at the distinctive characteristics between neuronal subtypes to understand which ar emore vulnerable to α-Synuclein aggregation and how this in turn could impact the entire circuit signaling. View the original preprint.
Article
Dopamine transporter and synaptic vesicle sorting defects initiate auxilin-linked Parkinson’s disease
Preprint: Auxilin helps in recycling of synaptic vesicles to facilitate neurotransmission and loss of auxilin is associated with PD. The authors show auxilin knockout mice exhibit typical PD pathology, dopamine transport is disrupted due to slower dopamine reuptake kinetics, and that macroautophagy and defective synaptic vesicle sorting contributes to dopamine dyshomeostasis.
Article
ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2
Published: 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. View original preprint.
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Article
In situ structural analysis reveals membrane shape transitions during autophagosome formation
Preprint: A hallmark of PD is the failure of quality control mechanisms in the cell, such as autophagy. The authors combined cell biology with correlative cryo-electron tomography in yeast cells to show a high resolution stepwise structural progression of autophagosome biogenesis. Further, they revealed the organelle interactome for growing autophagosomes.
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Protocol
Collection of protocols for paper: “Glucocerebrosidase, a Parkinson´s disease-associated protein, is imported into mitochondria and regulates complex I assembly and function”
This is a collection of protocols used in a recent pre-print by the Deleidi Lab, Team Schapira. You can access pre-print at https://doi.org/10.21203/rs.3.rs-1521848/v1
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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
Integrated multi-cohort analysis of the Parkinson’s disease gut metagenome
Preprint: Here, the fecal metagenomes of those living with PD compared to others in the household were profiled from 4 geographically-distinct sites across 3 continents. The question was whether there were any specific PD-associated signatures in gut microbiome that are either enriched or depleted in PD.
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
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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Protocol
Crystallization, data collection and structure solution of PxP-VAB
Protocol lists the steps to obtain PxP(Mcp1ct)-VABct crystals, X-ray diffraction data acquisition and obtaining the structure solution using molecular replacement with a model generated by AlphaFold2.
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Article
Endoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration
Review: Several mutations of genes that encode proteins localized at the endoplasmic reticulum membrane contact sites result in familial neurodegenerative diseases. Here, the authors provide an overview of such diseases, with a specific focus on proteins that directly or indirectly impact lipid transport.
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Article
Lysosomal dysfunction in neurodegeneration: emerging concepts and methods
Review: This review summarizes key technological advances that have led to a better understanding of the contribution of the lysosome to neurodegeneration and highlights key questions to be addressed moving forward.
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Protocol
Design and preparation of synthetic reference peptides for APP/Aβ TOMAHAQ proteomics, version 2
This protocol describes the design and preparation of synthetic reference peptides for APP/Aβ TOMAHAQ proteomics.
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