Aberrant microRNA expression in the brains of neurodegenerative diseases: miR‐29a decreased in Alzheimer disease brains targets neurone navigator 3

Neuropathology and Applied Neurobiology - Tập 36 Số 4 - Trang 320-330 - 2010
Mao Shioya1, Shinya Obayashi2, Hiroko Tabunoki2, Kunimasa Arima3, Yumiko Saito4, T. Ishida5, Jun‐ichi Satoh2
1Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
2Department of Bioinformatics and Molecular Neuropathology, Meiji, Pharmaceutical University
3Department of Psychiatry, National Center Hospital, NCNP,
4Department of Laboratory Medicine, National Center Hospital, NCNP, Tokyo, and
5Department of Pathology and Laboratory Medicine, Kohnodai Hospital, International Medical Center, Chiba, Japan

Tóm tắt

M. Shioya, S. Obayashi, H. Tabunoki, K. Arima, Y. Saito, T. Ishida and J. Satoh (2010) Neuropathology and Applied Neurobiology36, 320–330
Aberrant microRNA expression in the brains of neurodegenerative diseases: miR‐29a decreased in Alzheimer disease brains targets neurone navigator 3 Aims: MicroRNAs (miRNAs) are small non‐coding RNAs that regulate translational repression of target mRNAs. Accumulating evidence indicates that various miRNAs, expressed in a spatially and temporally controlled that manner in the brain plays a key role in neuronal development. However, at present, the pathological implication of aberrant miRNA expression in neurodegenerative events remains largely unknown. To identify miRNAs closely associated with neurodegeneration, we performed miRNA expression profiling of brain tissues of various neurodegenerative diseases. Methods: We initially studied the frontal cortex derived from three amyotrophic lateral sclerosis patients by using a microarray of 723 human miRNAs. This was followed by enlargement of study population with quantitative RT‐PCR analysis (n = 21). Results: By microarray analysis, we identified up‐regulation of miR‐29a, miR‐29b and miR‐338‐3p in amyotrophic lateral sclerosis brains, but due to a great interindividual variation, we could not validate these results by quantitative RT‐PCR. However, we found significant down‐regulation of miR‐29a in Alzheimer disease (AD) brains. The database search on TargetScan, PicTar and miRBase Target identified neurone navigator 3 (NAV3), a regulator of axon guidance, as a principal target of miR‐29a, and actually NAV3 mRNA levels were elevated in AD brains. MiR‐29a‐mediated down‐regulation of NAV3 was verified by the luciferase reporter assay. By immunohistochemistry, NAV3 expression was most evidently enhanced in degenerating pyramidal neurones in the cerebral cortex of AD. Conclusions: These observations suggest the hypothesis that underexpression of miR‐29a affects neurodegenerative processes by enhancing neuronal NAV3 expression in AD brains.

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Neuropathology and Applied Neurobiology

Tập 36 Số 4

320-330

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