GIRK2 - a G protein-coupled potassium channel that stabilizes resting potential

• Encoded by the KCNJ6 gene, which is upregulated in Down Syndrome and causes enhanced neuronal inhibition
• This is likely why persons with Down Syndrome have hippocampal-dependent learning impairments

Olig1 and Olig2 - transcription factors

• Regulate neurogenesis of GABAergic interneurons
• Increased expression of these two factors causes an increase in inhibitory neurons

DYRK1A - a dendritic protein

• Associated with GTPase dynamin
• Involved with synaptic vesicle recycling and membrane trafficking
• Modulates cAMP response element binding protein, which is involved in synaptic plasticity
• Increased expression of DYRK1A gene causes impaired spatial learning by impairing retrieval of synaptic proteins
• Interacts with synaptojanin 1, which is regulated by the Down Syndrome Critical Region gene 1 (DSCR1) and is a phosphotase required for synaptic vesicle endocytosis

DOPEY2 gene

• Regulates cortical cell density
• The increased amount seen in persons with Down Syndrome likely leads to abnormal cortical layering

SIM2 gene

• Transcriptional regulator that controls shh (sonic hedgehog) expression, which controls cell growth and differentiation
• Increased expression leads to mild learning impairment and decreased sensitivity to pain

TPRD protein

• Regulates neurite growth
• Increased expression seen in Down Syndrome inhibits neurite extension, leading to abnormal cortical layering

Amyloid Precursor Protein (APP gene)

• Located on chromosome 21, so triplication in Down Syndrome causes an increase in this gene
• Causes the plaque build-up seen in Alzheimer’s Disease, so the increased amount of APP gene in Down Syndrome is likely why these persons are likely to develop the disease so early in life

SOD1 - a copper-zinc (Cu-Zn) superoxide dismutase, which is an enzyme that’s important for inactivating oxygen free radicals

• Increased expression of this enzyme causes impaired long-term potentiation (LTP) and a decrease in protein clearance through the ubiquitin proteasome system

S100ꞵ - secreted glial calcium binding protein that's often associated with blood vessels

• Amplified in Down Syndrome and Alzheimer’s Disease
• Increased expression leads to changes in dendritic spine density in the hippocampus and impairments in spatial learning, which suggests that some cognitive symptoms in Down Syndrome are also caused by abnormal glial-neuronal interactions