Cause or Effect: Misregulation of microRNA Pathways in Neurodegeneration

Department of Neurology, University of Massachusetts Medical School Worcester, MA, USA.
Frontiers in Neuroscience (Impact Factor: 3.66). 04/2012; 6:48. DOI: 10.3389/fnins.2012.00048
Source: PubMed


During normal aging or neurodegenerative diseases, neuronal survival and function depend on protein homeostasis, which is regulated by multiple mechanisms, including the microRNA (miRNA) pathway. In different cells types, the absence of Dicer, a key miRNA processing enzyme, leads to neurodegeneration through cell-autonomous and non-cell-autonomous mechanisms. Loss of certain miRNAs also causes neurodegeneration in some model organisms. On the other hand, miRNA expression is misregulated in patients with different neurodegenerative diseases. Thus, the miRNA pathway appears to be essential in the pathogenesis of several age-dependent neurodegenerative conditions; however, our understanding of the underlying mechanism remains rudimentary. The precise causal relationships between specific miRNAs and neurodegeneration in humans need to be further investigated.

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    • "Recently miRNAs have been identified as crucial regulators of immune cell development and function. Deregulated miRNAs contribute to the development of various diseases, for example, cancer, cardiovascular, or neurological diseases (Bonauer et al., 2010; Gascon and Gao, 2012; Thum, 2012). Neurodegeneration is characterized by neuronal loss of specific neuronal circuits associated with cognitive and motor functions and by changes in miRNA levels in the nervous tissue and in the periphery. "
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    • "Moreover, it was recently proposed that specific RBPs or miR- NAs might be secreted from stressed motoneurons to stimulate defence mechanisms in astrocytes or endothelial cells (Aparicio-Erriu and Prehn, 2012; Gascon and Gao, 2012). This indicates that perturbed homeostasis of RBPs or miR- NAs, and the consequent changes in RNA metabolism may play a central role in neurodegenerative processes (Aparicio- Erriu and Prehn, 2012; Gascon and Gao, 2012; Kapeli and Yeo, 2012). Taken together, we feel that the present collection of reviews on the mRNA life cycle in normal brain function and malfunction provides a timely update by leading researchers to reflect recent developments in key technologies , and summarizes the current understanding and future directions for the studies of mRNA metabolism in the brain. "

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    • "MiRNAs are small noncoding RNAs that regulate gene expression post-transcriptionally by degrading their target mRNAs or repressing their translation [19], [20]. Although potential involvement of miRNAs in neurodegeneration has been increasingly appreciated, information about their regulation and function in diseased human neurons remains scarce [21]. "
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