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Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3.
Neuropathol Appl Neurobiol. 2010 Jun; 36(4):320-30.NA

Abstract

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.

Authors+Show Affiliations

Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20202123

Citation

Shioya, M, et al. "Aberrant microRNA Expression in the Brains of Neurodegenerative Diseases: miR-29a Decreased in Alzheimer Disease Brains Targets Neurone Navigator 3." Neuropathology and Applied Neurobiology, vol. 36, no. 4, 2010, pp. 320-30.
Shioya M, Obayashi S, Tabunoki H, et al. Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3. Neuropathol Appl Neurobiol. 2010;36(4):320-30.
Shioya, M., Obayashi, S., Tabunoki, H., Arima, K., Saito, Y., Ishida, T., & Satoh, J. (2010). Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3. Neuropathology and Applied Neurobiology, 36(4), 320-30. https://doi.org/10.1111/j.1365-2990.2010.01076.x
Shioya M, et al. Aberrant microRNA Expression in the Brains of Neurodegenerative Diseases: miR-29a Decreased in Alzheimer Disease Brains Targets Neurone Navigator 3. Neuropathol Appl Neurobiol. 2010;36(4):320-30. PubMed PMID: 20202123.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3. AU - Shioya,M, AU - Obayashi,S, AU - Tabunoki,H, AU - Arima,K, AU - Saito,Y, AU - Ishida,T, AU - Satoh,J, Y1 - 2010/02/25/ PY - 2010/3/6/entrez PY - 2010/3/6/pubmed PY - 2010/10/12/medline SP - 320 EP - 30 JF - Neuropathology and applied neurobiology JO - Neuropathol Appl Neurobiol VL - 36 IS - 4 N2 - 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. SN - 1365-2990 UR - https://www.unboundmedicine.com/medline/citation/20202123/Aberrant_microRNA_expression_in_the_brains_of_neurodegenerative_diseases:_miR_29a_decreased_in_Alzheimer_disease_brains_targets_neurone_navigator_3_ L2 - https://doi.org/10.1111/j.1365-2990.2010.01076.x DB - PRIME DP - Unbound Medicine ER -