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- Title
In situ continuous Dopa supply by responsive artificial enzyme for the treatment of Parkinson's disease.
- Authors
Fang, Xiao; Yuan, Meng; Zhao, Fang; Yu, Aoling; Lin, Qianying; Li, Shiqing; Li, Huichen; Wang, Xinyang; Yu, Yanbin; Wang, Xin; Lin, Qitian; Lu, Chunhua; Yang, Huanghao
- 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. Oral dihydroxyphenylalanine (Dopa) administration to replenish neuronal dopamine is a treatment for Parkinson's disease but induces fluctuations in plasma Dopa levels. Here the authors report a nucleic acid-based responsive artificial enzyme (FNA-Fe3O4) for in situ continuous Dopa production.
- Subjects
SYNTHETIC enzymes; DOPAMINE receptors; PARKINSON'S disease; DOPA; APTAMERS; BLOOD-brain barrier disorders; TRANSFERRIN receptors; TYROSINE hydroxylase
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-38323-w