Dr. Shumin Duan’s group published in Brain

On March 1, 2019, Brain published a study from Dr. Shumin Duan’s research group. The study, entitled “CD73-derived adenosine controls inflammation and neurodegeneration by modulating dopamine signaling”, investigated how adenosine metabolism pathway regulates microglia-mediated neuroinflammation and affects the progression of a Parkinson disease model.

Microglia-mediated neuroinflammation is implicated in the progression and exacerbation of a wide range of neurodegenerative disorders. However, mechanisms underlying the endogenous regulation of neuroinflammation remain elusive. Parkinson’s disease is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and prominent neuroinflammation. Increased activity of A_2AR signalling has been observed in Parkinson’s disease and A_2AR antagonism exhibited beneficial effects in the disease model and preclinical trials. However, little is known about whether enhanced A_2AR signalling controls neuroinflammation to affect the disease progression and where the adenosine resource leading to enhanced A_2AR signalling comes from.

In this study, Duan’s group presented the evidence that the ectonucleotidase CD73-derived adenosine activates A_2AR and enhances pro-inflammatory responses in microglia. Moreover, upregulated CD73 and A_2AR in Parkinson’s disease models promote neuroinflammation detrimental to dopaminergic neurons. Knockout of CD73 reduces the adenosine production and plays a neuroprotective role in Parkinson’s disease model by attenuating neuroinflammation. These data suggest that targeting nucleotide metabolic pathways to limit adenosine production and neuroinflammation might be a promising therapeutic strategy for Parkinson’s disease.

The first author of this paper is the PhD student Fan Meng. The corresponding authors are Shumin Duan and Zhihua Gao. This work was supported by basic research program of Ministry of Technology of China, Natural Science Foundation of China.

Link to the article：https://academic.oup.com/brain/article/142/3/700/5303235?guestAccessKey=9d41f9a7-13d0-4115-9f05-f0e3afc467a1

A model depicting the role of CD73-produced adenosine formation and A_2AR signalling in microglia-mediated neuroinflammation and neuronal degeneration.