Aethlon Medical Inc (AEMD)

[ANESRI]

Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells (Mad Cow Disease!)

http://nar.oxfordjournals.org/content/early/2012/09/08/nar.gks832.full


In summary, our results strongly support the hypothesis that exosomes released from prion-infected neuronal cells have a distinct miRNA signature that may be utilized for the identification of prion infection. This signature comprises significant increases in let-7 b, let-7i, miR-128 a, miR-21, miR-222, miR-29 b, miR-342-3 p and miR-424 with decreased miR-146 a detection and agrees to some extent to previously reported miRNA changes detected in brains of terminally infected mouse and primate models of prion disease, and sporadic CJD samples (17,18).

Evaluation of our exosomal miRNA signature in circulating exosomes derived from clinical plasma samples from sporadic and variant forms of human prion disease and in animal models infected with different prion strains will be the subject of our further studies. Importantly, it has been shown the miRNAs deregulated in prion-infected exosomes identified in this study have also been detected in circulating exosomes isolated from human serum samples (14), and that neither have currently been detected in disease-associated exosomes in the current literature and a search of ExoCarta database (58), suggesting that this miRNA signature has significant and specific diagnostic potential. However, it should be noted that our study also identified other ncRNAs and mRNA fragments (Supplementary Figure S1) that may also be deregulated in exosomes released from prion-infected neuronal cells. Furthermore, it has been identified that extracellular miRNA released from cells into plasma can associate in two populations, both dependent and independent of exosomes either bound to AGO2 (59–61) or high-density lipoproteins (62). Therefore, targeted exosomal purification strategies for enrichment of circulating miRNA biomarkers may be required to increase biomarker sensitivity (14,15,23). This research also has potential diagnostic implications for other neurodegenerative diseases in which exosomes have been identified to play a role including Alzheimer’s disease (63–65), amyotrophic lateral sclerosis (66) and Parkinson’s disease (67).

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