The Role of Exosomes in Stemness and Neurodegenerative Diseases—Chemoresistant-Cancer Therapeutics and Phytochemicals

Abstract

Exosomes exhibit a wide range of biological properties and functions in the living organisms. They are nanometric vehicles and used for delivering drugs, as they are biocompatible and minimally immunogenic. Exosomal secretions derived from cancer cells contribute to metastasis, immortality, angiogenesis, tissue invasion, stemness and chemo/radio-resistance. Exosome-derived microRNAs (miRNAs) and long non-coding RNAs (lnc RNAs) are involved in the pathophysiology of cancers and neurodegenerative diseases. For instance, exosomes derived from mesenchymal stromal cells, astrocytes, macrophages, and acute myeloid leukemia (AML) cells are involved in the cancer progression and stemness as they induce chemotherapeutic drug resistance in several cancer cells. This review covered the recent research advances in understanding the role of exosomes in cancer progression, metastasis, angiogenesis, stemness and drug resistance by illustrating the modulatory effects of exosomal cargo (ex. miRNA, lncRNAs, etc.) on cell signaling pathways involved in cancer progression and cancer stem cell growth and development. Recent reports have implicated exosomes even in the treatment of several cancers. For instance, exosomes-loaded with novel anti-cancer drugs such as phytochemicals, tumor-targeting proteins, anticancer peptides, nucleic acids are known to interfere with drug resistance pathways in several cancer cell lines. In addition, this review depicted the need to develop exosome-based novel diagnostic biomarkers for early detection of cancers and neurodegenerative disease. Furthermore, the role of exosomes in stroke and oxidative stress-mediated neurodegenerative diseases including Alzheimer’s disease (AD), and Parkinson’s disease (PD) is also discussed in this article.

Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

“…With the introduction of pasteurization of milk combined with the widespread availability of refrigeration technology, MEX unnoticeably entered the human food chain, modify the dietary exposome and disturb epigenetic regulation of the milk consumer. Thus, exosomes significantly contribute to the pathogenesis, progression and therapy of neurodegenerative diseases [ 150 , 342 , 343 ] and T2D [ 344 , 345 , 346 ]. Future research investigating MEX early impact on α -syn homeostasis during the physiological breastfeeding period and their long-term abuse in the pathogenesis of neurodegenerative diseases and T2D might offer new perspectives for the prevention and treatment of these common and related diseases of Western civilization ( Table 3 ).…”

The interplay between m6A modification and non-coding RNA in cancer stemness modulation: mechanisms, signaling pathways, and clinical implications

“…In addition, aberrant levels of lncRNAs could also determine the invasive and metastatic capacities of cancer cells, and lncRNA SNHG12 was a promising biomarker with clinical potential in many cancers including GC, NSCLC, and bladder cancer, because of its high stability and abundantly expression in multiple tumors 146 . Some exosome-derived lncRNAs were involved in the modulation of cancer stemness aspects such as chemotherapeutic drug resistance 147 . Additionally, exosomal lncRNAs derived from tumors were suitable candidates for non-invasive diagnosis.…”

Exosomes as Drug Delivery Systems: Endogenous Nanovehicles for Treatment of Systemic Lupus Erythematosus

“…Apart from the natural cargos of exosomes (miRNAs, siRNAs, DNAs, proteins, etc. ), their excellent biological properties have driven their use as drug delivery systems of synthetic compounds (see [ 126 ] for review). The carriage of chemical drugs by exosomes is being exploited mainly in cancer, using chemotherapy agents as cargos.…”