Global microRNA Expression Profiling of Caenorhabditis elegans Parkinson's Disease Models

Abstract

MicroRNAs (miRNAs) play an important role in human brain development and maintenance. To search for miRNAs that may be involved in the pathogenesis of Parkinsons disease (PD), we utilized miRNA microarrays to identify potential gene expression changes in 115 annotated miRNAs in PD-associated Caenorhabditis elegans models that either overexpress human A53T alpha-synuclein or have mutations within the vesicular catecholamine transporter (cat-1) or parkin (pdr-1) ortholog. Here, we show that 12 specific miRNAs are differentially regulated in the animals overexpressing alpha-synuclein, five in cat-1, and three in the pdr-1 mutants. The family of miR-64 and miR-65 are co-underexpressed in the alpha-synuclein transgenic and cat-1 strains, and members of let-7 family co-underexpressed in the alpha-synuclein and pdr-1 strains; mdl-1 and ptc-1 genes are target candidates for miR-64 and miR-65 and are overexpressed in alpha-synuclein transgenic as well as miR-64/65 (tm3711) knockout animals. These results indicate that miRNAs are differentially expressed in C. elegans PD models and suggest a role for these molecules in disease pathogenesis.

Identification of aberrant circulating miRNAs in Parkinson's disease plasma samples

“…Upregulation of let‐7 impairs glucose homeostasis and results in degeneration of neurons, while its downregulation leads to cancer (Shamsuzzama, Haque, & Nazir, 2016). let‐7 family members were underexpressed in the PD‐associated Caenorhabditis elegans models that either overexpress human A53T alpha‐synuclein or have mutations within parkin (pdr‐1) ortholog (Asikainen et al., 2010). Consistent with the literature, decreased levels of let‐7a and let‐7f in the plasma of PD were determined in our analysis.…”

Let-7, MiR-98 and MiR-181 as Biomarkers for Cancer and Schizophrenia

“…However, regarding Parkinson's Disease (PD), it is mentioned that in a Caenorhabditis elegans model let-7 is down-regulated in strains bearing a typical mutation in alphasynuclein gene (A53T) and in strains with mutations in the pdr-1 gene [20]. Moreover, increased levels of let-7 were found to attenuate pathogenic LRRK2 effects, a molecule which is very frequently mutated in both familial and sporadic PD [21].…”

Epigenetic Landscape of Parkinson's Disease: Emerging Role in Disease Mechanisms and Therapeutic Modalities

“…In transgenic mice overexpressing human A30P α-synuclein, the levels of miR-10a, -10b, -212, -132 and −495 were found to follow an altered expression pattern compared to non-transgenic littermates [40]. In yet another study that analyzed the differential expression of miRNAs in human α-synuclein transgenic Caenorhabditis elegans, the expression of 12 miRNAs was altered, including miR-64, and miR-65 and those of the let-7 family [41]. However, human orthologs of these microRNAs are not yet known.…”