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.
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.
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.
LRRK2-mutant microglia and neuromelanin synergize to drive dopaminergic neurodegeneration in an iPSC-based Parkinson’s disease model
PD is a neurodegenerative disorder characterized by the loss of neuromelanin (NM)-containing dopamine neurons. This work highlights NM-activated microglia’s role in PD progression, and provides a model for testing therapeutic targets.
Adeno-associated viral vectors for modeling Parkinson’s disease in non-human primates
The lack of adequate animal models of PD represents the main barrier to preclinical therapies to succeed in clinical trials. However, by novel generations of viral vectors coding for different forms of a-syn species and related genes.
Standardised TruAI Automated Quantification of Intracellular Neuromelanin Granules in Human Brain Tissue Sections
To standardise and automate the quantitation of human-unique neuromelanin granules in catecholamine neurons in post-mortem tissue sections from healthy individuals at different ages to understand any changes in these granules with age.
Longitudinal neuromelanin changes in prodromal and early Parkinson’s disease in humans and rat model
Results in animals and humans show that neuromelanin-sensitive-MRI is a marker of the intracellular neuromelanin accumulation and then of neuronal degeneration and originates mainly from T1 reduction effect of neuromelanin.
Sex-dimorphic effects of neuromelanin buildup in rodent nigral dopamine neurons: implications for sex-biased vulnerability in Parkinson’s disease
Neuromelanin (NM) is pigment accumulating with age in human SNpc dopamine (DA) neurons. This study discloses unrealized NM effects within nigral DA neurons, advancing our comprehension of sex-specific features shaping sex-biased vulnerability to PD.
Introducing PIGMO, a novel PIGmented MOuse model of Parkinson’s disease
There is a pressing need for the development of animal models of PD that properly mimic the its cardinal features. Here an AAV engineered to bypass the blood-brain barrier and coding for the human tyrosinase gene is used to generate the PIGMO model.
A molecular atlas of cell-type specific signatures in the parkinsonian striatum
Progressive dopamine loss in PD affects striatum cells differently. Transcriptomic analysis in mouse and human models reveals changes in neuronal and glial populations, highlighting resilient and vulnerable cell types for potential new treatments.
LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons
PD LRRK2 influences the effects of haloperidol, a common antipsychotic, on striatal indirect pathway neurons. Inhibiting LRRK2 kinase activity reduces haloperidol’s motor side effects, suggesting a way to ease antipsychotic side effects.
