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

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.