Exosomes and microRNAs in the treatment of in vivo and in vitro models of Parkinson’s disease: A narrative literature review

ABSTRACT: Parkinson's disease is a chronic neurodegenerative disorder affecting about 1% of the population over 60 years of age. The disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, with a significant decrease of dopamine in the striatum, and the increase of misfolded α-synuclein in the cytoplasm of the surviving dopaminergic neurons. Progression of the disease to multiple brain regions, including the olfactory bulb, brain stem, and cerebral cortex, is due to the intercellular transmission of the misfolded α-synuclein. The clinical features of Parkinson's disease involve non-motor symptoms such as depression, sleep disturbances, loss of smell, constipation, fatigue, and cognitive impairments, and motor symptoms that include tremor, rigidity, bradykinesia, postural instability, and gait disturbances. Parkinson's disease is often misdiagnosed due to the difficulty of clinical diagnosis. At present, no Parkinson's disease-modifying therapies exist, and drugs, surgery and exercise can only improve the early clinical symptoms of Parkinson's disease. There is an urgent need for early diagnosis and biomarkers together with therapeutic strategies aimed at early-stage intervention and identifying novel drug targets that address prodromal and established forms of the disease. This article is a narrative literature review of exosomes and microRNAs treatment in models of Parkinson's disease. In the in vivo studies of Parkinson's disease reviewed, exosomes from various sources ameliorated behavioral and cognitive deficits, lowered inflammation and α-synuclein levels in brain tissues, and protected dopaminergic neurons. Loading exosomes with microRNA mimics (e.g., miR-188-3p, miR-133b) or inhibitors (e.g., miR-184 antisense oligodeoxynucleotide, miR-137 antagomir) improved outcomes in the in vivo models of Parkinson's disease, while miRNA mimics (e.g., miR-188-3p, miR-30a-3p, miR-181c-5p, miR-23b-3p, miR-320a) or inhibitors (e.g., miR-184 antisense oligodeoxynucleotide) improved outcomes in the in vitro models. Thus, administration of exosomes could become an important treatment modality for Parkinson's disease. Future studies should incorporate older animals and more females to better model human populations.