Table 1.

Selected studies investigating neurological and neuropsychiatric disorders using human iPSC-derived 3D organoids.

Disease	Organoid Type	Days of Differentiation	Phenotype and Rescue	Unique Experimental Feature	Protocol
Timothy Syndrome [41]	Ventral and dorsal forebrain, assembloids	4 weeks	GABAergic interneuron abnormalities: altered saltation frequency and shorter saltation length; phenotype rescue by pharmacological modulation of l-type calcium channels	Forebrain assembloids with labelling of specific cell type (Dlxi1/2b::eGFP)	[42]
Autism Spectrum Disorder [43]	Dorsal forebrain	6 weeks	Transcriptome dysregulation: FOXG1 upregulation; increased production of NPCs and GABAergic neurons; rescue by shRNA attenuation of FOXG1 expression	Lentiviral-mediated expression of shRNA-FOXG1	[23]
Miller-Dieker Syndrome [44]	Forebrain	4 weeks	Smaller organoids with reduced neuroepithelial loops, impaired vRG divisions, disrupted cortical niche; rescue by gene re-expression or β-catenin activation	Doxycycline-inducible overexpression of LIS1 gene	[45,46]
Autosomal recessive primary microcephaly [22]	Undirected	~3 weeks	Altered vRG morphology and orientation, smaller organoids; rescue by shRNA for CDK5RAP2	Electroporation-mediated overexpression of CDK5RAP2 and shRNA-CDK5RAP2	[22]
Hypoxic injury [47]	Forebrain	~11 weeks	Disruption of intermediate progenitors in SVZ; impaired UPR pathway activation and premature neuronal differentiation; rescue by stress response inhibitor (ISRIB)	Gas control chamber and needle-type fiber-optic microsensor to reproduce and monitor low oxygen exposure	[42]
Zika virus infection (ZIKV) [29]	Forebrain	~3 months	Smaller organoids with reduced thickness and increased ventricular lumen, ZIKV-induced cell apoptosis	ZIKV strains: MR766 and FSS13025 (99% amino acid sequence homology to Brazilian ZIKV)	[29]
Cytomegalovirus infection (CMV) [48]	Undirected	8 weeks	Reduced cell proliferation, necrosis, vacuolar and cystic degeneration; impaired cortical lamination	Organoid differentiation from CMV-infected hiPSCs	[46]
Creutzfeld-jakob disease (CJD) [49]	Undirected	5 months	Slow metabolism, protease-resistant PrP deposition, acquired prion seeding activity, increased astrocyte activation	Organoids inoculation with human brain homogenates from sporadic CJD subtypes	[46]
Brain tumors [50]	Forebrain	~4 months	Glioma-like with poor glial differentiation, high cell proliferation, disorganized architecture and downregulation of PI3K-AKT, RAS pathways; CNS-PTEN-like with WNT, TGFβ, and TP53 upregulation; tumor invasiveness upon in vivo transplantation; partial rescue in glioma by EGFR-inhibitors	Electroporation-mediated plasmid nucleofection with overexpression of MYC/inhibition of tumor suppressor genes	[22]