Molecular and cellular alterations in Down syndrome: toward the identification of targets for therapeutics

Abstract

Down syndrome is a complex disease that has challenged molecular and cellular research for more than 50 years. Understanding the molecular bases of morphological, cellular, and functional alterations resulting from the presence of an additional complete chromosome 21 would aid in targeting specific genes and pathways for rescuing some phenotypes. Recently, progress has been made by characterization of brain alterations in mouse models of Down syndrome. This review will highlight the main molecular and cellular findings recently described for these models, particularly with respect to their relationship to Down syndrome phenotypes.

Figure 1

HSA21 (with main cytogenetic bands) and its ortholog segments in the mouse genome (MMU16, MMU17 and MMU10) are indicated. Main mouse models and those reported in this review are indicated in black for human genes, and in gray for mouse genes. Models with cDNA constructs are indicated in italics. Representation of their localisation is not to scale. Tc1 [32]; TghAPP [33]; TgSYNJ1 [54]; TgITSN1 [55]; TgRCAN1-L [56]; TgYAC152F7 [34]; hBACTgDYRK1A [24]; TgPCP4 [38]; TghCBS60.4 [57]; Ts65Dn [22]; Ts1Cje [23]; Ts1RhR [58]; TgSynj1 [54]; TgDyrk1a [59]; mBACTgDyrk1a [25]; Dup(16)Yu, Dup(17)Yu and Dup(10)Yu [29, 31]; Ts1Yah [30].