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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Selective loss of Primary Cilia and Neurotrophic Signaling in G51D α-Synuclein Mice Highlights a Common Pathway to Parkinson’s Disease
G51D α-synuclein mice mimic disease symptoms, showing cilia loss in specific neurons and impaired neurotrophic signaling, contributing to disease progression. This highlights the role of ciliary dysfunction in Parkinson’s.
Role of autophagy pathway in Parkinson’s disease and related Genetic Neurological disorders
The authors provide a comprehensive overview of the general importance of autophagy in Parkinson’s disease (PD) and related disorders of the central nervous system (CNS).
Parkinson’s VPS35[D620N] mutation induces LRRK2-mediated lysosomal association of RILPL1 and TMEM55B
This study uncovers a pathway through which dysfunctional lysosomes resulting from the VPS35[D620N] mutation recruit and activate LRRK2 on the lysosomal surface, driving assembly of the RILPL1-TMEM55B complex.
Isotope tracing in health and disease
Here, the authors review recent work utilizing metabolic tracing to study health and disease, and highlight its application to interrogate subcellular, intercellular, and in vivo metabolism.
PTEN-induced kinase 1 (PINK1) and Parkin: Unlocking a mitochondrial quality control pathway linked to Parkinson’s disease
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.
Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain
Pathogenic mutations in LRRK2 can 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.
Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis
The data support a model in which localization drives PPM1H substrate selection and centriolar PPM1H is critical for regulation of Rab GTPase-regulated ciliogenesis.
Whole proteome copy number dataset in primary mouse cortical neurons
The authors provide a proteomic reference dataset that has been generated to identify proteins and quantify their level of expression in primary mouse cortical neurons.
Golgi-IP, a novel tool for multimodal analysis of Golgi molecular content
The authors develop a method for the rapid capture of intact Golgi via Golgi immunoprecipitation. Using high-resolution mass spectrometry, the approach allows the unbiased characterization of the Golgi proteome, metabolome, and lipidome.
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain
Leucine-rich-repeat-kinase 1 (LRRK1) and its homologue LRRK2 are multidomain kinases. Here, the authors study the mechanism controlling LRRK1 activity and reveal a novel unexpected activation mechanism.
A feed-forward pathway drives LRRK2 kinase membrane recruitment and activation
LRRK2 interacts with Rab8A and Rab10 at specific binding sites, enhancing LRRK2 kinase activity on membranes. This feed-forward pathway regulates LRRK2 activation and substrate phosphorylation.
Genome-wide screen reveals Rab12 GTPase as a critical activator of Parkinson’s disease-linked LRRK2 kinase
The data support a model in which Rab12 binding to a new site in the LRRK2 Armadillo domain activates LRRK2 kinase for Rab phosphorylation
Impact of 100 LRRK2 variants linked to Parkinson’s Disease on kinase activity and microtubule binding
This study systematically investigates 100 LRRK2 variants linked to PD, and provides rationale for variant carrier inclusion/exclusion in ongoing and future LRRK2 inhibitor clinical trials.
Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2
This study reports the cryo-EM structure of LRRK2-Rab29 complexes and provides rationale for LRRK2 membrane recruitment and activation.
LRRK2 phosphorylation of Rab GTPases in Parkinson’s disease
Review: This paper highlights new findings related to LRRK2-mediated phosphorylation of Rab GTPases and their consequences.
