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
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.
Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders
Reelin levels might modulate the numbers of striatal interneurons and the density of the nigrostriatal dopaminergic projections, suggesting that these changes may be involved in the protection of Reelin against neuropsychiatric disorders.
Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions
The authors developed an iPSC toolbox utilizing piggyBac-based or targeted transgenes to rapidly induce CNS cells with concomitant expression of aggregation-prone proteins.
Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates
A new NHP PD model was developed by inducing neuromelanin (NM) accumulation in dopaminergic neurons, leading to synucleinopathy and neuron degeneration similar to human PD neuropathology. Lowering NM levels may offer PD therapeutic strategies.
Modelling human brain-wide pigmentation in rodents recapitulates age-related multisystem neurodegenerative deficits
Authors describe an animal model of human-like neuromelanin pigmentation. The animals display age-related neuronal dysfunction and degeneration affecting numerous brain circuits and body tissues.
In vivo reduction of age-dependent neuromelanin accumulation mitigates features of Parkinson’s disease
Humanized rodents with neuromelanin can develop Parkinson's symptoms. Reducing neuromelanin accumulation mitigates PD features, showing a link between NM levels and disease pathology.
Non-ablative disease-modifying effects of magnetic resonance-guided focused ultrasound in neuromelanin-producing parkinsonian rodents
The authors' findings indicate that tFUS treatment applied at prodromal/early disease stages provides extended structural and functional preservation of the nigrostriatal pathway in neuromelanin-producing parkinsonian rats.
Local diffusion in the extracellular space of the brain
The authors highlight emerging technological advances to respectively interrogate and model diffusion through the ECS, and point out how these may contribute in resolving the remaining enigmas of the ECS.
