Regulation of RAGE splicing by hnRNP A1 and Tra2β-1 and its potential role in AD pathogenesis.

The receptor for advanced glycation end products gene expresses two major alternative splicing isoforms, full-length membrane-bound and secretory duanyu1648 Both isoforms play important roles in Alzheimer's disease (AD) pathogenesis, either via interaction of with β-amyloid peptide (Aβ) or inhibition of the signaling pathway. In the present study, we showed that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and Transformer2β-1 (Tra2β-1) were involved in the alternative splicing of mduanyu1648 and Functionally, two factors had an antagonistic effect on the regulation. Glucose deprivation induced an increased ratio of via up-regulation of hnRNP A1 and down-regulation of Tra2β-1. Moreover, the ratios of mduanyu1648/esduanyu1648 and hnRNP A1/Tra2β-1 were increased in peripheral blood mononuclear cells from AD patients. The results provide a molecular basis for altered splicing of mduanyu1648 and in AD pathogenesis. The receptor for advanced glycation end products (duanyu1648) gene expresses two major alternative splicing isoforms, membrane-bound duanyu1648 (mduanyu1648) and secretory duanyu1648 (esduanyu1648). Both isoforms play important roles in Alzheimer's disease (AD) pathogenesis. Mechanism for imbalanced expression of these two isoforms in AD brain remains elusive. We proposed here a hypothetic model to illustrate that impaired glucose metabolism in AD brain may increase the expression of splicing protein hnRNP A1 and reduce Tra2β-1, which cause the imbalanced expression of mduanyu1648 and esduanyu1648.

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