Summary of project PR002121
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002121. The data can be accessed directly via it's Project DOI: 10.21228/M8FV6T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002121 |
| Project DOI: | doi: 10.21228/M8FV6T |
| Project Title: | Genetic screening and metabolomics identify glial adenosine metabolism as a therapeutic target in Parkinson’s disease |
| Project Type: | Metabolomic profiling of Parkinson's Disease Drosophila model |
| Project Summary: | Parkinson’s disease (PD) is the second most common neurodegenerative disorder and lacks disease-modifying therapies. We developed a Drosophila model for identifying novel glial- based therapeutic targets for PD. Human α-synuclein is expressed in neurons and individual genes are independently knocked down in glia. We performed a forward genetic screen, knocking down the entire Drosophila kinome in glia in α-synuclein expressing flies. Among the top hits were five genes (Ak1, Ak6, Adk1, Adk2, and awd) involved in adenosine metabolism. Knockdown of each gene improved locomotor dysfunction, rescued neurodegeneration, and increased brain adenosine levels. We determined that the mechanism of neuroprotection involves adenosine itself, as opposed to a downstream metabolite. We dove deeper into the mechanism for one gene, Ak1, finding rescue of dopaminergic neuron loss, α-synuclein aggregation, and bioenergetic dysfunction after glial Ak1 knockdown. We performed metabolomics in Drosophila and in human PD patients, allowing us to comprehensively characterize changes in purine metabolism and identify potential biomarkers of dysfunctional adenosine metabolism in people. These experiments support glial adenosine as a novel therapeutic target in PD. |
| Institute: | Broad Institute of MIT and Harvard |
| Last Name: | Avila-Pacheco |
| First Name: | Julian |
| Address: | 415 Main Street |
| Email: | jravilap@broadinstitute.org |
| Phone: | (617) 714-1729 |
| Contributors: | Sodders M, Kumari N, Okorie E, Shen M, Lakhani M, Marathi A, Sarkar S, Scherzer CR, Clish C, Feany MB, Olsen AL, Bullock K, Pierce K, Dennis C, Jeanfavre D, Avila-Pacheco, J |
Summary of all studies in project PR002121
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003438 | Unbiased genetic screening and metabolomics identifies glial adenosine metabolism as a therapeutic target in Parkinson’s disease | Drosophila melanogaster | Broad Institute of MIT and Harvard | MS | 2024-08-29 | 1 | 12 | Uploaded data (6.5G)* |
