RNA Interference
RNA interference is a mechanism by which cells utilize short bits of non-coding RNA (microRNA and small interfering RNA) to suppress other genes. A possible pathogenic role of RNA interference mechanisms in PD is not clear, but some initial reports suggest the possibility (Nelson et al., 2008; Sethupathy and Collins, 2008). A specific microRNA, miR-133b, appears to be involved in dopamine neuron development and is reduced in brains of people with PD (Kim et al., 2007). Individuals with a particular polymorphism in a microRNA binding site of the FGF20 RNA 3’ untranslated region have been associated with greater PD risk; the variant is hypothesized to disrupt microRNA suppression of FGF20 leading to downstream toxicity (Wang et al., 2008).
Use of RNA intereference to target specific disease-associated gene transcription has been suggested as a possible therapeutic strategy (Gonzales-Alegre, 2007).
Reference:
Nelson PT, Wang WX, Rajeev BW. MicroRNAs (miRNAs) in neurodegenerative diseases. Brain Pathol. 2008;18(1):130-8.
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Sethupathy P, Collins FS. MicroRNA target site polymorphisms and human disease. Trends Genet. 2008;24(10):489-97.
Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV, Murchison E, et al. A MicroRNA feedback circuit in midbrain dopamine neurons. Science. 2007;317(5842):1220-4.
Wang G, van der Walt JM, Mayhew G, Li YJ, Züchner S, Scott WK, et al. Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. Am J Hum Genet. 2008;82(2):283-9.
Gonzalez-Alegre P. Therapeutic RNA interference for neurodegenerative diseases: From promise to progress. Pharmacol Ther. 2007;114(1):34-55.
Responses:
22 Jul 2009 10:47 AM EST
