Table 2: Applications of iNeurons in disease modeling and drug discovery

Type of iNeurons

Disease features

Cell origin

Reprogramming factors

Diseases model

Ref.

DAs

Progressive degeneration and death of dopaminergic neuron (DA) in the substantia niagra region of the midbrain.

MEFs/HFFs

Ascl1, Nurr1, Lmx1a

Parkinson's disease

[129]

HFFs

Ascl1, Brn2, Myt1l, Lmx1a, FoxA2

Parkinson's disease

[115]

HFFs

Ascl1, Ngn2, Sox2, Nurr1, Pitx3

Parkinson's disease

[130]

MNs

Progressive degeneration and death of motor neuron (MN) in the cortex, brain stem and spinal cord.

HEFs

Ascl1, Brn2, Myt1l, Hb9, lsl1, Lhx3, Ngn2, NeuroD1

ALS/SMA

[131]

Patient-derived GAs

Genetic mutation of SCN1A and impaired psychomotor development and ataxia.

Fibroblasts

Ascl1, Brn2, Myt1l, NeuroD1, Olig2, Zic1, rtTA

Dravet syndrome

[132]

RGC

Accelerated death of retinal ganglion cells (RGC) leads to progressive visual field loss and eventual blindness.

MEFs

Ascl1, Brn3b, Ngn2

Glaucoma

[133]

iNeurons with MAPT mutation

Cause behavioural and executive impairement.

Human skin fibroblasts

Ascl1, Brn2, Myt1l, Lmx1a, FoxA2

Frontotemporal lobar degeneration

[134]

iNeurons with CACNA1C mutation

Cause social interaction, communication and behavioural impairement.

Human dermal fibroblasts

Ascl1, Pou3f2, Myt1l

Autism spectrum disorder

[135]

iNeurons with abnormal amyloid-β peptide production

Aggregation and accumulation of amyloid-β peptide, which is forming amyloid plaques in the brain.

Human foreskin/skin fibroblasts

VPA, CHIR, Repsox, Forskolin, SP600125, GO6983, Y-27632, Dorsomorphin

Alzheimer’s disease

[118]

Abbreviations: MEFs, mouse embryo fibroblasts; HFFs, human foreskin fibroblasts