RGD Reference Report - MicroRNA profiling of Parkinson's disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function. - Rat Genome Database

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MicroRNA profiling of Parkinson's disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function.

Authors: Minones-Moyano, E  Porta, S  Escaramis, G  Rabionet, R  Iraola, S  Kagerbauer, B  Espinosa-Parrilla, Y  Ferrer, I  Estivill, X  Marti, E 
Citation: Minones-Moyano E, etal., Hum Mol Genet. 2011 Aug 1;20(15):3067-78. doi: 10.1093/hmg/ddr210. Epub 2011 May 10.
RGD ID: 10755477
Pubmed: PMID:21558425   (View Abstract at PubMed)
DOI: DOI:10.1093/hmg/ddr210   (Journal Full-text)

MicroRNAs (miRNAs) are post-transcriptional gene expression regulators, playing key roles in neuronal development, plasticity and disease. Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by the presence of protein inclusions or Lewy bodies and a progressive loss of dopaminergic neurons in the midbrain. Here, we have evaluated miRNA expression deregulation in PD brain samples. MiRNA expression profiling revealed decreased expression of miR-34b and miR-34c in brain areas with variable neuropathological affectation at clinical (motor) stages (Braak stages 4 and 5) of the disease, including the amygdala, frontal cortex, substantia nigra and cerebellum. Furthermore, misregulation of miR-34b/c was detected in pre-motor stages (stages 1-3) of the disease, and thus in cases that did not receive any PD-related treatment during life. Depletion of miR-34b or miR-34c in differentiated SH-SY5Y dopaminergic neuronal cells resulted in a moderate reduction in cell viability that was accompanied by altered mitochondrial function and dynamics, oxidative stress and reduction in total cellular adenosin triphosphate content. MiR-34b/c downregulation was coupled to a decrease in the expression of DJ1 and Parkin, two proteins associated to familial forms of PD that also have a role in idiopathic cases. Accordingly, DJ1 and Parkin expression was reduced in PD brain samples displaying strong miR-34b/c downregulation. We propose that early deregulation of miR-34b/c in PD triggers downstream transcriptome alterations underlying mitochondrial dysfunction and oxidative stress, which ultimately compromise cell viability. A better understanding of the cellular pathways controlling and/or controlled by miR-34b/c should allow identification of targets for development of therapeutic approaches.



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Objects Annotated

Genes (Rattus norvegicus)
Mir34b  (microRNA 34b)
Mir34c  (microRNA 34c)

Genes (Mus musculus)
Mir34b  (microRNA 34b)
Mir34c  (microRNA 34c)

Genes (Homo sapiens)
MIR34B  (microRNA 34b)
MIR34C  (microRNA 34c)


Additional Information