Microcephaly
|
CDK5RAP2
|
Human iPSCs
|
Cerebral cortex
|
Smaller neuroepithelial regions, altered spindle orientation of radial glial cells, abundant neuronal outgrowth, smaller organoid size
|
Heterozygous nonsense mutation in CDK5RAP2
|
Reintroducing CDK5RAP2 protein
|
[34]
|
Impaired brain growth
|
ZIKV
|
Human iPSCs
|
Forebrain
|
Increased cell death and suppressed proliferation of neural progenitors, decreased neuronal layer thickness and organoid size, enlarged lumen/ventricles
|
-
|
-
|
[36]
|
Impaired brain growth
|
ZIKV
|
Human ESCs
|
Cerebral cortex
|
Attenuated brain organoid growth
|
TLR3-mediated dysregulation of neurogenesis
|
TLR3 inhibitor
|
[57]
|
Impaired brain growth
|
ZIKV
|
Human iPSCs
|
Cerebral cortex
|
Reduced viability and growth of neural progenitor cells, smaller brain organoid size
|
-
|
-
|
[58]
|
Impaired brain growth
|
ZIKV
|
Human ESCs/iPSCs
|
Cerebral cortex
|
Increased apoptosis in neural progenitors, reduction of prolifration zone, disrupted cortical layers
|
-
|
-
|
[59]
|
Impaired brain growth
|
Cocaine
|
Human ESCs
|
Neocortex
|
Proliferation inhibition of neuroepithelial progenitors, premature neuronal differentiation, reduction in cortical plate formation
|
CYP3A5-mediated cocaine oxidative metabolism
|
CYP3A5 inhibitor/Knockdown of CYP3A5
|
[40]
|
Autism spectrum disorder/macrocephalic phenotype
|
-
|
Human iPSCs
|
Dorsal telencephalon
|
Increased progenitor cell proliferation, enhanced synaptic maturation, overproduction of GABAergic inhibitory neurons
|
Overexpression of transcription factor FOXG1
|
Knockdown of FOXG1
|
[86]
|
Early-onset familial Alzheimer’s
|
APP
|
Human iPSCs
|
Neocortex
|
β-amyloid (Aβ) aggregation, hyperphosphorylated Tau (pTau), endosome abnormalities
|
APP duplication
|
β- and γ-secretase inhibitors
|
[93]
|