In situ continuous Dopa supply by responsive artificial enzyme for the treatment of Parkinson’s disease

Xiao Fang, Meng Yuan, Fang Zhao, Aoling Yu, Qianying Lin, Shiqing Li, Huichen Li, Xinyang Wang, Yanbin Yu, Xin Wang, Qitian Lin, Chunhua Lu () and Huanghao Yang ()
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Xiao Fang: Fuzhou University
Meng Yuan: Fuzhou University
Fang Zhao: Fuzhou University
Aoling Yu: Fuzhou University
Qianying Lin: Fuzhou University
Shiqing Li: Fuzhou University
Huichen Li: Fuzhou University
Xinyang Wang: Fuzhou University
Yanbin Yu: Fuzhou University
Xin Wang: Fuzhou University
Qitian Lin: Fuzhou University
Chunhua Lu: Fuzhou University
Huanghao Yang: Fuzhou University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Oral dihydroxyphenylalanine (Dopa) administration to replenish neuronal dopamine remains the most effective treatment for Parkinson’s disease (PD). However, unlike the continuous and steady dopamine signaling in normal neurons, oral Dopa induces dramatic fluctuations in plasma Dopa levels, leading to Dopa-induced dyskinesia. Herein, we report a functional nucleic acid-based responsive artificial enzyme (FNA-Fe3O4) for in situ continuous Dopa production. FNA-Fe3O4 can cross the blood-brain barrier and target diseased neurons relying on transferrin receptor aptamer. Then, FNA-Fe3O4 responds to overexpressed α-synuclein mRNA in diseased neurons for antisense oligonucleotide treatment and fluorescence imaging, while converting to tyrosine aptamer-based artificial enzyme (Apt-Fe3O4) that mimics tyrosine hydroxylase for in situ continuous Dopa production. In vivo FNA-Fe3O4 treatment results in recovery of Dopa and dopamine levels and decrease of pathological overexpressed α-synuclein in PD mice model, thus ameliorating motor symptoms and memory deficits. The presented functional nucleic acid-based responsive artificial enzyme strategy provides a more neuron friendly approach for the diagnosis and treatment of PD.

Date: 2023
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DOI: 10.1038/s41467-023-38323-w

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