Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cells
Protein tau plays a pivotal role in the pathophysiology of Alzheimer's disease, where its hyperphos-phorylation promotes aggregation and microtubule destabilization. Tau undergoes alternative splicing which generates six isoforms in the human brain, due to inclusion/exclusion of exons 2, 3 and...
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| Format: | Article |
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Academia Brasileira de Ciências
2014-12-01
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| Series: | Anais da Academia Brasileira de Ciências |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652014000401927&lng=en&tlng=en |
| _version_ | 1811270020473290752 |
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| author | TERESA LAGUNES MARISOL HERRERA-RIVERO MARÍA ELENA HERNÁNDEZ-AGUILAR GONZALO E. ARANDA-ABREU |
| author_facet | TERESA LAGUNES MARISOL HERRERA-RIVERO MARÍA ELENA HERNÁNDEZ-AGUILAR GONZALO E. ARANDA-ABREU |
| author_sort | TERESA LAGUNES |
| collection | DOAJ |
| description | Protein tau plays a pivotal role in the pathophysiology of Alzheimer's disease, where its hyperphos-phorylation promotes aggregation and microtubule destabilization. Tau undergoes alternative splicing which generates six isoforms in the human brain, due to inclusion/exclusion of exons 2, 3 and 10. Dysregulation of the splicing process of tau exon 10 is sufficient to cause tauopathy and has shown to be influenced by beta-amyloid peptides, but splicing of other exons is less studied. We studied the effects of beta-amyloid(42) in the alternative splicing of tau exons 2/3 and 6, using untreated and Nerve Growth Factor-induced PC12 cells. Beta-amyloid exposure caused formed cell processes to retract in differentiated cells and altered the expression of exons 2/3 in both undifferentiated and differentiated cells. Expression of exon 6 was repressed in undifferentiated cells only. Our results suggest that beta-amyloid interferes with the splicing process of exons 2/3, favoring their exclusion and thus the expression of immature tau isoforms that are less efficient in stabilizing microtubules and may also be more prone to hyperphosphorylation. The molecular mechanism for this amyloid-tau interaction remains to be determined, but may have potential implications for the understanding of the underlying neuropathological processes in Alzheimer's disease. |
| first_indexed | 2024-04-12T21:53:27Z |
| format | Article |
| id | doaj.art-d9c7671692284154b436b8f084b073ba |
| institution | Directory Open Access Journal |
| issn | 1678-2690 |
| language | English |
| last_indexed | 2024-04-12T21:53:27Z |
| publishDate | 2014-12-01 |
| publisher | Academia Brasileira de Ciências |
| record_format | Article |
| series | Anais da Academia Brasileira de Ciências |
| spelling | doaj.art-d9c7671692284154b436b8f084b073ba2022-12-22T03:15:25ZengAcademia Brasileira de CiênciasAnais da Academia Brasileira de Ciências1678-26902014-12-018641927193410.1590/0001-3765201420130333S0001-37652014000401927Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cellsTERESA LAGUNESMARISOL HERRERA-RIVEROMARÍA ELENA HERNÁNDEZ-AGUILARGONZALO E. ARANDA-ABREUProtein tau plays a pivotal role in the pathophysiology of Alzheimer's disease, where its hyperphos-phorylation promotes aggregation and microtubule destabilization. Tau undergoes alternative splicing which generates six isoforms in the human brain, due to inclusion/exclusion of exons 2, 3 and 10. Dysregulation of the splicing process of tau exon 10 is sufficient to cause tauopathy and has shown to be influenced by beta-amyloid peptides, but splicing of other exons is less studied. We studied the effects of beta-amyloid(42) in the alternative splicing of tau exons 2/3 and 6, using untreated and Nerve Growth Factor-induced PC12 cells. Beta-amyloid exposure caused formed cell processes to retract in differentiated cells and altered the expression of exons 2/3 in both undifferentiated and differentiated cells. Expression of exon 6 was repressed in undifferentiated cells only. Our results suggest that beta-amyloid interferes with the splicing process of exons 2/3, favoring their exclusion and thus the expression of immature tau isoforms that are less efficient in stabilizing microtubules and may also be more prone to hyperphosphorylation. The molecular mechanism for this amyloid-tau interaction remains to be determined, but may have potential implications for the understanding of the underlying neuropathological processes in Alzheimer's disease.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652014000401927&lng=en&tlng=enDoença de Alzheimerpeptídeo amilóideregulação de splicingisoformas tau |
| spellingShingle | TERESA LAGUNES MARISOL HERRERA-RIVERO MARÍA ELENA HERNÁNDEZ-AGUILAR GONZALO E. ARANDA-ABREU Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cells Anais da Academia Brasileira de Ciências Doença de Alzheimer peptídeo amilóide regulação de splicing isoformas tau |
| title | Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cells |
| title_full | Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cells |
| title_fullStr | Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cells |
| title_full_unstemmed | Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cells |
| title_short | Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cells |
| title_sort | abeta 1 42 induces abnormal alternative splicing of tau exons 2 3 in ngf induced pc12 cells |
| topic | Doença de Alzheimer peptídeo amilóide regulação de splicing isoformas tau |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652014000401927&lng=en&tlng=en |
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