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Table 3 Clinical relevance of the core DHN to dementia through biomarker-guided analysis

From: A network model of genomic hormone interactions underlying dementia and its translational validation through serendipitous off-target effect

Target candidate Pathway membership Disease association Biomarker type Brain tissue specificity Cell-type specificity
MAPK3 Alzheimer’s disease, Prion disease, Type II diabetes mellitus, Insulin signaling pathway, Long-term potentiation Autism CSF increased levels AD (PMID: 22145083, 19625747), Phosphorylation (PMID: 19233276, 16920298, 17612901), Alterations in lymphoblasts of AD patients (PMID: 19158936) Left ventricle, Right ventricle, Brain stem Microglia, Astrocytes, Neurons
NOS1 Alzheimer's disease, Long-term depression, Calcium signaling pathway Parkinson's disease, Alzheimer's disease, Diabetes Mellitus type II Nitric oxide overproduction (PMID: 20804853), nNOS signaling initiated in interneurons (PMID: 16758165), Increased expression of nNOS isoforms in astrocytes (PMID: 12384247) Substantia nigra, Forebrain, cerebral white matter, Limbic system Astrocytes, Neurons
CREB1 Huntington's disease, Cholinergic synapse Alzheimer's disease Impaired CREB phosphorylation (PMID:22119240) Substantia nigra, Brain stem, Sub-commissural organ, Brain ventricle, Cerebral gray matter, Cerebral white matter, Forebrain, limbic system Hippocampal neurons, Dendate gyrus
JUN GnRH signaling pathway, Neurotrophin signaling pathway, MAPK signaling pathway Cognitive performance Prolonged expression of c-Jun (PMID:8774439), Increased immuno-reactivity (PMID:8313943) Sub-commissural organ, Brain ventricle, Cerebral gray and white matter Neurons, Microglia, Substantia nigra