Exosomes regulate neurogenesis and circuit assembly

Sharma, P. L.; Mesci, Pinar; Carromeu, Cassiano; McClatchy, Daniel R.; Schiapparelli, Lucio; Yates, John R.; Muotri, Alysson R.; Cline, Hollis T.

doi:10.1073/pnas.1902513116

Cited by 194 publications

(181 citation statements)

References 36 publications

(57 reference statements)

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“…Exosomes have been described as a novel form of information exchange between cells with the capability to influence various cellular functions [29]. The ability of exosomes to regulate and influence a diverse range of biological processes within the nervous system has been reported [41,42]. Neuronal signals through neurotransmitter glutamate could regulate exosome release by oligodendrocytes [43].…”

Section: Neuronal and Non-neuronal Cell Cross-talk Mediated By Exosomesmentioning

confidence: 99%

Role of Exosomes in Cancer-Related Cognitive Impairment

Koh

Tan

Toh

et al. 2020

IJMS

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A decline in cognitive function following cancer treatment is one of the most commonly reported post-treatment symptoms among patients with cancer and those in remission, and include memory, processing speed, and executive function. A clear understanding of cognitive impairment as a result of cancer and its therapy can be obtained by delineating structural and functional changes using brain imaging studies and neurocognitive assessments. There is also a need to determine the underlying mechanisms and pathways that impact the brain and affect cognitive functioning in cancer survivors. Exosomes are small cell-derived vesicles formed by the inward budding of multivesicular bodies, and are released into the extracellular environment via an exocytic pathway. Growing evidence suggests that exosomes contribute to various physiological and pathological conditions, including neurological processes such as synaptic plasticity, neuronal stress response, cell-to-cell communication, and neurogenesis. In this review, we summarize the relationship between exosomes and cancer-related cognitive impairment. Unraveling exosomes' actions and effects on the microenvironment of the brain, which impacts cognitive functioning, is critical for the development of exosome-based therapeutics for cancer-related cognitive impairment.Int. J. Mol. Sci. 2020, 21, 2755 2 of 16 attention, learning, and executive function [10]. CRCI adversely affects cancer patients and survivors, causing distress and reduced quality of life, and impacts many facets of their daily lives [11]. CRCI is complicated by many factors including the direct effects of cancer, genetic predisposition (e.g., carrier of apolipoprotein E type epsilon 4 allele [12] and brain-derived neurotrophic factor Met allele [13]), comorbidities independent of the actual disease, and/or treatments or combinations of treatments administered for the disease [14].Efforts to better understand cancer-and cancer-therapy-associated cognitive impairment have relied on methods ranging from cognitive functioning assessment to imaging technologies on brain structure and function (e.g., magnetic resonance imaging scan). However, these approaches may be limited to help us understand the etiology and pathophysiology of cognitive dysfunction. The emerging application of the use of liquid biopsies (e.g., plasma and cerebrospinal fluid) as a strategy for biomarker discovery to detect, assess and monitor CRCI is fast-expanding and evolving [15,16]. In published literature, studies have revealed that genetics and neurobiological and immunological mechanisms may be involved in the biogenesis and development of CRCI. Preclinical studies have also provided insights into the pathophysiological mechanisms underlying CRCI, including neurotoxicity and inflammatory factors, which were shown to be responsible for CRCI [17]. Nevertheless, the underlying mechanisms of CRCI have yet to be established. While the role of exosomes in cancer has been well-documented [18][19][20], the role of cancer exosomes and their ability ...

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Section: Neuronal and Non-neuronal Cell Cross-talk Mediated By Exosomesmentioning

confidence: 99%

Role of Exosomes in Cancer-Related Cognitive Impairment

Koh

Tan

Toh

et al. 2020

IJMS

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“…These data suggest that malignant disease either potentiates nerve recruitment (as compared to normal ovary and benign tumors) or elaborates functional circuits that are more complex. Recent work by Sharma et al shows that during development, neurons respond to sEVs with increased proliferation (neurogenesis) and enhanced neural circuit formation [77]. Moreover, neuronal activity promotes brain growth [78].…”

Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating nerves create an electro-physiologically active microenvironment and contribute to treatment resistance

Kovács

Vermeer

Madeo

et al. 2020

Preprint

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Patients with densely innervated tumors do poorly as compared to those with sparsely innervated disease. Why some tumors heavily recruit nerves while others do not, remains unknown as does the functional contribution of tumor-infiltrating nerves to cancer. Moreover, while patients receive chemotherapeutic treatment, whether these drugs affect nerve recruitment has not been tested. Using a murine model of ovarian cancer, we show that tumor-infiltrating sensory nerves potentiate tumor growth, decrease survival, and contribute to treatment resistance. Furthermore, matched patient samples show significantly increased tumor innervation following chemotherapy. In vitro analysis of tumor-released extracellular vesicles (sEVs) shows they harbor neurite outgrowth activity. These data suggest that chemotherapy may alter sEV cargo, endowing it with robust nerve recruiting capacity.

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“…The study on exosomes is continually growing, to yield valuable information regarding their intrinsic properties in regulating complex intracellular pathways, including those underlying neurological disorders [65]. In contrast to AAV vectors, the exosomes administration ensures the functional delivery of their cargo with minimal interference from the immune system [66] and has proven to be safe and well-tolerated.…”

Section: Exosomes: Natural Shuttles To Deliver Exogenous Acids Nucleimentioning

confidence: 99%

Development of New Strategies Using Extracellular Vesicles Loaded with Exogenous Nucleic Acid

Orefice

2020

Pharmaceutics

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Gene therapy is a therapeutic strategy of delivering foreign genetic material (encoding for an important protein) into a patient’s target cell to replace a defective gene. Nucleic acids are embedded within the adeno-associated virus (AAVs) vectors; however, preexisting immunity to AAVs remains a significant concern that impairs their clinical application. Extracellular vesicles (EVs) hold great potential for therapeutic applications as vectors of nucleic acids due to their endogenous intercellular communication functions through their cargo delivery, including lipids and proteins. So far, small RNAs (siRNA and micro (mi)RNA) have been mainly loaded into EVs to treat several diseases, but the potential use of EVs to load and deliver exogenous plasmid DNA has not been thoroughly described. This review provides a comprehensive overview of the principal methodologies currently employed to load foreign genetic material into EVs, highlighting the need to find the most effective strategies for their successful clinical translation.

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Exosomes regulate neurogenesis and circuit assembly

Cited by 194 publications

References 36 publications

Role of Exosomes in Cancer-Related Cognitive Impairment

Role of Exosomes in Cancer-Related Cognitive Impairment

Tumor-infiltrating nerves create an electro-physiologically active microenvironment and contribute to treatment resistance

Development of New Strategies Using Extracellular Vesicles Loaded with Exogenous Nucleic Acid

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