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.

Protocol

Collection of protocols of Team Deleidi used in the publication: “LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease”

Collection of protocols of Team Deleidi used in the publication: “LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease.”

Article

Mechanism of human PINK1 activation at the TOM complex in a reconstituted system

Preprint: The authors demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These molecular findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD.

Article

Response to: “Is Gauchian genotyping of GBA1 variants reliable?”

Preprint: To understand the cause of these discrepancies, the team reviewed their data, and concluded that they are misinterpreting Gauchian results in 8 of the 11 discrepant samples, and incorrectly using Gauchian to analyze low-coverage 1kGP samples.

Article

The annotation and function of the Parkinson’s and Gaucher disease-linked gene GBA1 has been concealed by its protein-coding pseudogene GBAP1

Here, the authors identify novel transcripts from both GBA1 and GBAP1, including protein-coding transcripts that are translated in vitro and detected in proteomic data, but that lack GCase activity.

Article

3D bioprinting of human neural tissues with functional connectivity

Probing how human neural networks operate is hindered by the lack of reliable human neural tissues amenable to the dynamic functional assessment of neural circuits. Team Scherzer developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter.

Article

Synaptic location is a determinant of the detrimental effects of α-synuclein pathology to glutamatergic transmission in the basolateral amygdala

αSyn expression is restricted in a subset of glutamatergic synapses in BLA and its aggregation decreases cortico-BLA transmission through both gained toxicity and loss of normal function. These results might be relevant to the reduced cortical control of amygdala function that has been associated with psychiatric deficits in PD.

Article

The pathogenesis of Parkinson’s disease

This review is the second in a series of three papers about Parkinson’s disease published in the Lancet.

Article

Alpha-synuclein overexpression can drive microbiome dysbiosis in mice

Growing evidence indicates that persons living with Parkinson’s disease (PD) have a unique composition of indigenous gut microbes. Here, the authors used a transgenic mouse strain, which overexpress wild-type human α-syn to test how the gut microbiome composition responds in this model of PD pathology during aging.

Article

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 possessing a ROC-CORA-CORB containing GTPase domain and phosphorylate distinct Rab proteins. LRRK1 loss of function mutations cause the bone disorder osteosclerotic metaphyseal dysplasia, whereas LRRK2 missense mutations that enhance kinase activity cause PD. Here, the authors study the mechanism controlling LRRK1 activity and reveal a novel unexpected activation mechanism. View preprint.

Article

Pseudogenes limit the identification of novel common transcripts generated by their parent genes

Preprint: Genetic analyses are often complicated by genomic sequences with high sequence similarity. Here, the authors examined the role of pseudogenes on transcriptomic analyses using GB1 and GBAP1 as examples.