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Research Article

A core-satellite-like nanoassembly reverses a decisive tyrosine hydroxylase loss in degenerative dopaminergic neurons

Ke Yao1,2,§, Jiamin Gan1,§, Di Zhao1, Mingding Li1, Xiaoquan Shen1, Yumin Yang2( ), Peijian Feng1( ), Qundong Shen1,3,4( )
Department of Polymer Science & Engineering and Key Laboratory of High-Performance Polymer Materials and Technology of MOE, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing 210023, China
Key Laboratory for Neuroregeneration of Jiangsu Province and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
Medical School of Nanjing University, Nanjing 210008, China
State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210023, China

§ Ke Yao and Jiamin Gan contributed equally to this work.

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Graphical Abstract

A core-satellite-like nanoassembly (PDA-AFn) not only elaborately regulates the iron homeostasis and redox microenvironment, but also utilizes excessive reactive oxygen species (ROS) and iron ions in the damaged neurons to supply extra dopamine and enhance tyrosine hydroxylase activity, and consequently restore the function of the degenerated neurons.

Abstract

In recent years, neurodegenerative diseases, such as Parkinson’s or Alzheimer’s diseases, are rapidly rising in prevalence. The main hallmark of Parkinson’s disease is the falling levels of neurotransmitter dopamine in the mid-brain with dopaminergic neurons losing. Typical therapeutic solutions, including drugs, deep brain stimulation, and cell transplantation, can only alleviate the symptoms of Parkinson’s disease. It is a tremendous challenge to reverse the function degeneration of the crucial dopaminergic neurons. Herein, we develop a core-satellite-like nanoassembly (PDA-AFn (by integrating polydopamine nanoparticles and apoferritin)) to raise the expression of tyrosine hydroxylase (TH), a rate-limiting enzyme in the formation of the dopamine. Both components in the nanoassembly could cooperate with each other, not only elaborately regulate the iron homeostasis and redox microenvironment, but also utilize excessive reactive oxygen species (ROS) and iron ions in the damaged neurons to supply extra dopamine and enhance TH activity, and consequently restore the function of the degenerated neurons. Remarkably, the nanoassembly-treatment relieves the dyskinesia and dramatical increases the tyrosine hydroxylase and dopamine level in the midbrain of Parkinson’s disease model mice. It is an explicit yet inspiring advance in treatment of the neurodegeneration.

Keywords

neurodegenerative diseasedopaminergic neuronstyrosine hydroxylaseapoferritinParkinson’s disease.

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Nano Research
Volume 16 Issue 7,
July 2023
Pages 9835-9847
DOI: 10.1007/s12274-023-5729-4
Cite this article:
Yao K, Gan J, Zhao D, et al. A core-satellite-like nanoassembly reverses a decisive tyrosine hydroxylase loss in degenerative dopaminergic neurons. Nano Research, 2023, 16(7): 9835-9847. https://doi.org/10.1007/s12274-023-5729-4
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Received: 21 February 2023
Revised: 06 April 2023
Accepted: 09 April 2023
Published: 09 May 2023
© Tsinghua University Press 2023
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