Potential Therapeutic Applications and Developments of Exosomes in Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease around the world. Current treatments alleviate the symptoms through the administration of drugs, including dopamine precursors, dopamine metabolism inhibitors, and activated dopamine agonists, but they cannot prevent the ongoing dopaminergic damage. One of the pivotal factors is the poor drug transport efficiency of crossing the blood–brain barrier, while studies reveal that exosomes are endogenous vesicles that are useful for drug delivery and disease diagnosis. As drug carriers, exosomes can not only deliver effective therapeutic drugs but also conquer difficulties such as biocompatibility, blood–brain barrier penetrability, metabolic stability, and target specificity. Exosomes have been successfully loaded with catalase, dopamine, catalase mRNA, and small interfering RNA for PD treatment and shown significant therapeutic effects. As diagnostic indicators (biomarkers), exosomes are more sensitive and reliable. They can reflect the pathological conditions and monitor disease progression. Exosomes from cerebrospinal fluid, plasma, serum, saliva, and urine are valuable biomarkers for PD diagnosis. This review mainly illuminates the association between exosomes and PD, sums up the therapeutic and diagnostic applications of exosomes in PD, and raises some critical remaining questions on the field. It is proposed that future investigations could be dedicated to exploiting a standard procedure to prepare large-scale exosomal carriers with high loading efficiency and new components of exosomes as biomarkers (mRNA; receptors), for better therapeutic and diagnostic options of PD.

A Neuron-Glial Model of Exosomal Release in the Onset and Progression of Alzheimer's Disease

“…Protein misfolding, oligomerization, and aggregation are responsible for the initiation of pathological disorders in the brain (Soto and Pritzkow, 2018 ). Nano-sized extracellular vesicles (exosomes) are believed to be key mediators in the transfer of cytotoxic proteins between the nerve cells, resulting in the spread of many neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Creutzfeldt-Jacob's disease (CJD) (Jiang et al, 2019 ; Luo et al, 2020 ; Zhang and Wang, 2020 ).…”

Enhanced Neuroprotective Effects of Epicatechin Gallate Encapsulated by Bovine Milk-Derived Exosomes against Parkinson’s Disease through Antiapoptosis and Antimitophagy

“…19 In a previous study, sonication was adopted because it was a common and effective method with convenience and high drug-loading efficiency. 27 ECG-Exo were successfully prepared by sonication in our study. It was reported the drug loading was around 10−40% (chemopreventive, chemotherapeutic) in Exo derived from bovine milk.…”

Exosomes in Parkinson: Revisiting Their Pathologic Role and Potential Applications

“…The drug can be loaded to EXOs to curtail these concerns, based on their ability to mediate the neuronal communication in the CNS and pass through the BBB [172]. EXOs could be harnessed to deliver CNS-acting drugs to treat and alleviate PD symptoms since they can adhere to the specified cell surface and release their cargoes [29,[173][174][175].…”