Table 1.
Physiological and pathogenic role of affected Hsa21 genes
| Hsa21 genes | Physiological role | Pathogenic role | Reference |
|---|---|---|---|
| OLIG1/OLIG2 | Implicated in neurogenesis and oligodendrogenesis | Causes GABAergic excitatory-inhibitory imbalance | Lu et al., 2002; Zhou & Anderson, 2002; Chakrabarti et al., 2010 |
| KCNJ6 | Effector protein for GABAB receptors; modulates potassium channel current and density | Contributes to enhanced GABAB signalling | Best et al., 2007; Best et al., 2011; Kleschevnikov et al., 2012 |
| SYNJ1 | Nerve terminal protein implicated in membrane trafficking and synaptic transmission | Inability to maintain stable GABAergic neurotransmission | Luthi et al., 2001 |
| DYRK1A | Regulates signalling and cell proliferation; involved in neurogenesis and neurodevelopment | Deregulates genes implicated in dendritic growth, cell pluripotency and embryonic stem cell fate; deregulates NFAT circuits and may cause enhanced Tau phosphorylation | Altafaj et al., 2001; Lepagnol-Bestel et al., 2009; Canzonetta et al., 2008; Arron et al., 2006; Jung et al., 2011 |
| RCAN1 | Inhibits calcineurin-dependent signalling pathways affecting development; modulates NMDAR activation | Decreases opening probability of NMDAR channel; deregulates NFAT circuits and may cause enhanced Tau phosphorylation | Arron et al., 2006; Jung et al., 2011 |
| DSCAM | Cell adhesion molecule with a critical role in dendrite morphology and neuronal wiring | Inhibits dendritic branching and causes aberrant synaptic plasticity; aberrant NMDA-mediated regulation of DSCAM local translation | Alves-Sampaio et al., 2010 |
| SIM2 | Transcriptional repressor implicated in synaptic plasticity and morphology | Reduces DBN1 levels causing morphological cytoskeletal changes at postsynaptic terminals in dendritic spines | Ooe et al., 2004; Hayashi et al., 1996 |
| SOD1 | Cytoplasmic protein implicated in oxidative stress | Reduces hippocampal neuronal progenitors and LTP; enhances sensitivity to degeneration and apoptosis; up-regulates GABAergic neurotransmission | Gahtan et al., 1998; Levkovitz et al., 1999 |
| APP | Cell surface receptor and transmembrane precursor protein that promotes transcriptional activation | Forms the protein basis of amyloid plaques prevalent in AD and DS; mechanism of action unknown | Rovelet-Lecrux et al., 2006; Netzer et al., 2010 |