31 August 2007. In today’s Science, Asa Abeliovich and colleagues at Columbia University in New York report that miRNAs, small regulatory RNAs that control messenger RNA degradation and play important roles in development, are critical to the maturation and survival of postmitotic neurons. Specifically, first author Jongpil Kim and coworkers show that mice lacking the machinery to produce mature miRNAs in dopaminergic neurons develop a progressive loss of neurons later in life, and eventually manifest a movement disorder resembling Parkinson disease. The work comes on the heels of Claudia Bagni’s recent paper establishing a role for noncoding, cytoplasmic RNAs (which are distinct from miRNAs) in regulating dopamine receptors and dopaminergic neurotransmission (see ARF related news story).
In an accompanying commentary, Sebastian Hebert and Bart De Strooper of the Katholieke Universiteit Leuven in Belgium consider the implications of the finding, including the possibility that changes in specific miRNAs might be found not only in PD, but also in other age-related neurodegenerative diseases including AD. For example, miRNA-related changes in expression of amyloid precursor protein or other AD-related genes could contribute to pathogenesis.
“The work by Kim et al. and other recent studies [Schratt et al., 2006; Bilen et al., 2006] herald a new area of exciting research in the field of neurodegenerative diseases,” they write. “Clinical studies will rapidly determine the extent to which miRNAs contribute to the pathogenesis of sporadic Parkinson and Alzheimer disease; however, the role of miRNAs as a potential therapeutic target remains a challenging question.”—Pat McCaffrey.
Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV, Murchison E, Hannon G, Abeliovich A. A microRNA feedback circuit in midbrain dopaminergic neurons. Science. 2007 Aug 31; 317:1220-1224. Abstract
Hebert SS, De Strooper B. Molecular biology. miRNAs in neurodegeneration. Science. 2007 Aug 31; 317:1179-1180. Abstract