Genetik tarama, glial adenozin metabolizmasını ve adenilat kinaz 1 inhibisyonu alfa-sinükleinopatide terapötik bir hedef olarak tanımlar.

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Neuronal α-synucleinopathies, including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), lack disease-modifying therapies. We developed a Drosophila model for identifying novel glial-based therapeutic targets for α-synucleinopathies. In this model, 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 increased brain adenosine levels, improved locomotor dysfunction, reduced α-synuclein oligomer levels, and rescued neurodegeneration. We determined that the mechanism of neuroprotection requires adenosine signaling through the neuronal adenosine receptor (AdoR) in Drosophila . These experiments support glial adenosine as a novel therapeutic target in PD.

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