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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Multi-omics reveal critical differentiation target for Parkinson’s Disease-vulnerable midbrain dopaminergic neurons
We describe a multiomic-guided strategy that enriches SOX6+ mDA neurons by combining enhancing Sonic Hedgehog agonism with prolonged Wnt activation. This work is a reproducible differentiation platform for generating the PD-susceptible mDA subtype
Striatal ensembles specify and control granular forelimb actions
The striatum plays a crucial role in controlling movements and learning. These results reveal specific ensembles of both D1- and D2-MSNs causally control specific ongoing actions, as granular as different muscle co-contractions of the same forelimb.
Matters arising: Forced Symmetry Artifacts in a Prohibitin Complex Structure
Lange et al. proposed a model for mitochondrial prohibitin complex with unequal subunit stoichiometry. Data suggests an asymmetric structure, questioning the validity of the proposed model. Care is needed in symmetry imposition in cryo-ET.
A Multimodal Atlas Reveals the Anatomical Distribution of Medium Spiny Neuron Subtypes and a Novel RGS6+ Population in the Primate Striatum
We combined single-nucleus multi-omic sequencing and high-plex spatial transcriptomics to build a comprehensive atlas of medium spiny neurons (MSNs) across the entire macaque striatum, revealing new MSN subtypes and their association with diseases.
Iron mishandling in the brain and periphery in Parkinson’s disease
The prodromal phase of Parkinson’s disease is complex. Gastrointestinal dysfunction and iron dysregulation may drive neurodegenerative risk. Identifying catalysts in the gut is crucial for developing disease-modifying therapies.
Microbiome signature of Parkinson disease in healthy and genetically at-risk individuals
Parkinson's disease (PD) is disabling and costly. *GBA1* variants increase PD risk. Gut microbiome changes can predict PD progression and identify those at risk, suggesting potential for disease modification through nutrition.
Pathway and gates for ATG2A-mediated lipid transport in autophagy
ATG2A ransfers lipids between donor and acceptor membranes leading to autophagosome formation. This study suggests that ATG2A is a lipid transporter gated at the N-terminus by blocking helices that, upon release, act as additional membrane tethers.
Reconstitution of multistep recruitment of ULK1 to membranes in autophagy
ULK1C and PI3KC3-C1 work together to start autophagy. This work establishes a stepwise pathway for recruitment of the ULK1 KD to the vicinity of the membrane surface downstream of PI3KC3-C1 to initiate autophagy.
Parkinson’s disease modeling in regenerative spiny mice (Acomys dimidiatus) captures key disease-relevant behavioral, histological, and molecular signatures
This paper models PD for the first time in a unique regenerative mammalian model, spiny mice, finding that 6-OHDA and αSyn PFFs induce robust pathology.
Adenosine in the brain: recent progress on detection, function and translation
Recent advancements have expanded our understanding of adenosine in the brain, revealing its role in regulating brain circuits for sleep, movement, cognition, and more.
Extracellular space diffusion modelling identifies distinct functional advantages of archetypical glutamatergic and GABAergic synapse geometries
We modelled extracellular diffusion in super-resolved images of live brain tissue neuropil. We found that extracellular space geometry shapes local diffusion and this has functional implications for signaling arising from synaptic spill-over.
A Novel α-Synuclein K58N Missense Variant in a Patient with Parkinson’s Disease
15% of cases of PD are linked to mutations in the SNCA gene. A novel K58N mutation in a patient showed typical PD symptoms, genetic testing, and biophysical studies revealing structural effects and abnormal cellular behavior of SNCA.
A framework for efficient CRISPRi-mediated silencing of retrotransposons in human pluripotent stem cells
This methods paper outlines silencing transposable elements in hiPSCs using CRISPRi. Describes gRNA design, validation via multiome approach. Enables functional studies on TE transcription in hiPSC models.
Proteome Landscapes Decode Organelle Vulnerabilities in cortical and dopaminergic-like induced neurons Across Lysosomal Storage Disorders
Lysosomal Storage Disorders impact lysosomal function and can be linked to Parkinson's Disease risk. LSD mutant cells show varied endolysosomal proteomes, with specific disruptions in neuronal cells.
Leucine Rich Repeat Kinase 2: Pathways to Parkinson’s Disease
Research on LRRK2 in Parkinson's disease has advanced, revealing how mutations activate the kinase, phosphorylate Rab proteins, disrupt cell functions like Hedgehog signaling, and contribute to the disease. LRRK2 inhibitors show promise for therapy.
