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Interplay Between Exosomes, microRNAs and Toll-Like Receptors in Brain Disorders

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Abstract

Extracellular vesicles (EVs), including exosomes, microvesicles and apoptotic bodies, participate in intercellular communication, and particularly, in paracrine and endocrine signalling. The EVs and their specific contents have been considered hallmarks of different diseases. It has been recently discovered that EVs can co-transport nucleic acids such as DNAs, ribosomal RNAs, circular RNAs (circRNAs), long noncoding RNAs (lnRNAs) and microRNAs (miRNAs). miRNAs are important regulators of gene expression at the post-transcriptional level, although they may also play other roles. Recent evidence supports the hypothesis that miRNAs can activate Toll-like receptors (TLRs) under certain circumstances. TLRs belong to a multigene family of immune system receptors and have been recently described in the nervous system. In the immune system, TLRs are important for the recognition of the invading microorganisms, whereas in the nervous system, they recognise endogenous ligands released by undifferentiated or necrotic/injured cells. In the neuronal disease field, TLRs activity has been associated with amyotrophic lateral sclerosis (ALS), stroke, Alzheimer’s and Parkinson’s disease. Herein, we reviewed the current knowledge of the relationship between miRNA release by EVs and the inflammation signalling triggered by TLRs in neighbouring cells or during long-distance cell-to-cell communication. We highlight novel aspects of this communication mechanism, offering a valuable insight into such pathways in health and disease.

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Funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, #2014/16711-6) and Universidade Federal do ABC.

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  1. Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil

    Vera Paschon, Silvia Honda Takada, Juliane Midori Ikebara, Erica Sousa, Reza Raeisossadati & Alexandre Hiroaki Kihara

  2. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, 05508-000, São Paulo, SP, Brazil

    Henning Ulrich

  3. Laboratório de Neurogenética, Universidade Federal do ABC, 112, Bloco Delta R. Arcturus 3, 09606-070, São Bernardo do Campo, SP, Brazil

    Vera Paschon & Alexandre Hiroaki Kihara

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  1. Vera Paschon
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Correspondence to Vera Paschon or Alexandre Hiroaki Kihara.

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Paschon, V., Takada, S.H., Ikebara, J.M. et al. Interplay Between Exosomes, microRNAs and Toll-Like Receptors in Brain Disorders. Mol Neurobiol 53, 2016–2028 (2016). https://doi.org/10.1007/s12035-015-9142-1

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