Table 2 Modeling neurological disorders with 3D brain organoids derived from human pluripotent stem cells

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]