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MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants.

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  • معلومة اضافية
    • Author-Supplied Keywords:
      Alzheimer's disease
      gene expression profiling
      microarrays
      tau 3R
      tau 4R
    • Abstract:
      Tau aggregation in neurofibrillary tangles is a pathological hallmark in tauopathies including Alzheimer's disease (AD). The predominant aggregation of certain MAPT (tau gene) isoforms, either the 4-repeat (4R tau) or the 3-repeat (3R tau) isoform has been widely described in tauopathies. Alterations of the 4R tau to 3R tau ratio may be a key for tau-related neurodegeneration. To study the biological consequences in expression between tau splicing isoforms 4R and 3R, we analyzed the main neurobiological effects of inclusion of the repeat region coded by exon 10 in MAPT. We compared the transcriptional profiles of the 4R tau isoforms to 3R tau isoforms using whole-genome gene expression profiling microarrays using human neuroblastoma SH-SY5Y cell lines overexpressing either human 4R tau or 3R tau isoforms. We identified 68 transcripts that differed significantly (at p< 0.001) between 4R and 3R isoforms as conditioned on a second variant, the so-called 2N inclusion. We extended these findings in a 2 × 2 ANOVA to examine interaction effects of these variants. Transcripts involved in embryonic development were downregulated when exon 10 was present, while transcripts related to outgrowth of neurites were generally upregulated. An important pathway implicated in AD also differed between the 3R and 4R cell lines, Wnt signaling. These studies demonstrate expression differences between MAPT isoforms 4R tau and 3R tau due to the inclusion/exclusion of the repeat region coded for by exon 10. Our data add to complex findings on the role of 3R/4R in normal and abnormal neuronal function and highlight several molecular mechanisms that might drive neurodegeneration, or perhaps, set the stage for it. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • Author Affiliations:
      1The Litwin-Zucker Research Center for Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, North Shore University Hospital, Manhasset, NY, USA
      2Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
    • ISSN:
      1387-2877
    • Accession Number:
      10.3233/JAD-2010-101155
    • Accession Number:
      56607133
  • Citations
    • ABNT:
      SHUFEN CHEN et al. MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants. Journal of Alzheimer’s Disease, [s. l.], v. 22, n. 4, p. 1313–1329, 2010. DOI 10.3233/JAD-2010-101155. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=56607133&custid=s8280428. Acesso em: 4 ago. 2020.
    • AMA:
      Shufen Chen, Townsend K, Goldberg TE, Davies P, Conejero-Goldberg C. MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants. Journal of Alzheimer’s Disease. 2010;22(4):1313-1329. doi:10.3233/JAD-2010-101155.
    • AMA11:
      Shufen Chen, Townsend K, Goldberg TE, Davies P, Conejero-Goldberg C. MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants. Journal of Alzheimer’s Disease. 2010;22(4):1313-1329. doi:10.3233/JAD-2010-101155
    • APA:
      Shufen Chen, Townsend, K., Goldberg, T. E., Davies, P., & Conejero-Goldberg, C. (2010). MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants. Journal of Alzheimer’s Disease, 22(4), 1313–1329. https://doi.org/10.3233/JAD-2010-101155
    • Chicago/Turabian: Author-Date:
      Shufen Chen, Kirk Townsend, Terry E. Goldberg, Peter Davies, and Concepcion Conejero-Goldberg. 2010. “MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants.” Journal of Alzheimer’s Disease 22 (4): 1313–29. doi:10.3233/JAD-2010-101155.
    • Harvard:
      Shufen Chen et al. (2010) ‘MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants’, Journal of Alzheimer’s Disease, 22(4), pp. 1313–1329. doi: 10.3233/JAD-2010-101155.
    • Harvard: Australian:
      Shufen Chen, Townsend, K, Goldberg, TE, Davies, P & Conejero-Goldberg, C 2010, ‘MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants’, Journal of Alzheimer’s Disease, vol. 22, no. 4, pp. 1313–1329, viewed 4 August 2020, .
    • MLA:
      Shufen Chen, et al. “MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants.” Journal of Alzheimer’s Disease, vol. 22, no. 4, Dec. 2010, pp. 1313–1329. EBSCOhost, doi:10.3233/JAD-2010-101155.
    • Chicago/Turabian: Humanities:
      Shufen Chen, Kirk Townsend, Terry E. Goldberg, Peter Davies, and Concepcion Conejero-Goldberg. “MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants.” Journal of Alzheimer’s Disease 22, no. 4 (December 29, 2010): 1313–29. doi:10.3233/JAD-2010-101155.
    • Vancouver/ICMJE:
      Shufen Chen, Townsend K, Goldberg TE, Davies P, Conejero-Goldberg C. MAPT Isoforms: Differential Transcriptional Profiles Related to 3R and 4R Splice Variants. Journal of Alzheimer’s Disease [Internet]. 2010 Dec 29 [cited 2020 Aug 4];22(4):1313–29. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=56607133&custid=s8280428