MicroRNAs in neurodegeneration

Temasek Life Sciences Laboratory, 1 Research Link, Singapore 117604, Singapore.
Current Opinion in Neurobiology (Impact Factor: 6.63). 09/2008; 18(3):292-6. DOI: 10.1016/j.conb.2008.07.001
Source: PubMed


microRNAs (miRNAs) act as post-transcriptional regulators of gene expression in diverse cellular and developmental processes. Many miRNAs are expressed specifically in the central nervous system, where they have roles in differentiation, neuronal survival, and potentially also in plasticity and learning. The absence of miRNAs in a variety of specific postmitotic neurons can lead to progressive loss of these neurons and behavioral defects reminiscent of the phenotypes seen in the pathologies of neurodegenerative diseases. Here, we review recent studies which provide a link between miRNA function and neurodegeneration. We also discuss evidence which might suggest involvement of miRNAs in the emergence or progression of neurodegenerative diseases.

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    • "MicroRNAs (miRNAs) are a class of small, nonproteincoding RNA molecules [18] [19]. They modulate translation of specific genes, allowing them to fine-tune protein expression and thus regulate different physiologic and pathologic cellular processes [20] [21] [22] [23] [24] [25] [26]. Because the expression of many different gene products can be regulated by an individual miRNA, they are attractive candidates for effective interventions aimed to suppress pathophysiologic cellular responses to injury and environmental changes [27] [28]. "

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    • "In terms of neurodegeneration, many studies have directly addressed the role of miRNAs in the development and regulation of the nervous system (reviewed in Schaefer et al., 2007; Bushati and Cohen, 2008; Barbato et al., 2009; Hebert and De Strooper, 2009; Martino et al., 2009; Roshan et al., 2009; Weinberg and Wood, 2009; Lau and de Strooper 2010). It has also been reported that the dysfunction of brain-enriched miRNAs specifically targeting and regulating the expression of disease-associated genes may lead to neurodegeneration and that disease-linked proteins may regulate the miRNA machinery (Savas et al., 2008; Gehrke et al., 2010; Esteller, 2011). "
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    • "Conditional knockout of the miRNA biosynthetic enzyme Dicer in the developing mouse brain has demonstrated that miRNAs have a critical role in neuronal survival in various brain regions [22], [23], [24], [25], including the hippocampus [26], [27], [28], [29]. Likewise, disruption of Dicer at later time points suggests that alterations in miRNA expression are associated with the degeneration of mature neurons in mice [30], [31]. Others have shown that miRNAs can play fundamentally important roles in more specific neurobiological processes such as proliferation, differentiation, neurite growth and apoptosis [8], [32], [33], [34]. "
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