Molecular advances in Down syndrome and their possible application in neurology

Abstract

This review examines recent advances in knowledge about Down’s Syndrome (DS), with emphasis on molecular therapy and its potential in the treatment of other disorders related with DS such as Alzheimer’s Disease (AD) and cognitive impairment. The close relationship between DS and early onset AD is well-known. DS, for which there is no specific treatment yet, is the main cause of mental disability worldwide and is caused by full or partial trisomy of chromosome 21. Over-expression of genes located in this chromosome is the main cause of DS, some of them are critical for the disease. For example, DYRK1A, a dual-specificity tyrosine phosphorylation-regulated kinase, has been strongly correlated with learning impairment associated with DS and the early onset AD. The pathogenesis of DYRK1A is by hyperphosprorylation of the amyloid precursor protein (APP) and the tubulin associated unit (Tau) directly related with the AD in non SD patients. Another potential application is that DS patients have a low risk of developing solid tumors, due to suppression of angiogenesis resulting from inhibition of the vascular endothelial growth factor (VEGF) via the inhibition of calcineurin pathway by DSCR-1 protein, that is over-expressed in the 21st chromosome. Molecular therapy for DS using two vasoactive intestinal peptides (NAP and SAL) is still at experimental level and has been tried only in murine models, but has shown considerable potential in the treatment of developmental delay and learning deficits in DS and other neurological disease.