Table 1.

Examples of neurodegenerative iPSC modeling

Disease	Cell type	Phenotype	References
Alzheimer’s disease	Neurons	Increased deposition of pathological markers amyloid-β and phosphorylated Tau protein Activated glycogen synthase kinase-3β Endosomal abnormalities	58, 125
Frontotemporal dementia	Motor and forebrain neurons	Impaired axonal transport C9ORF72 repeat region containing RNA foci Altered gene expression Diminished neuronal firing capacity	37, 72
Huntington’s disease	Neural precursor cells, forebrain and striatal neurons, astrocytes	Reduced survival Altered gene expression Altered cytoskeleton, adhesion, energetics and neurite outgrowth Reduced neuronal firing capacity Increased susceptibility to stressors Cytoplasmic, electron clear vacuoles in astrocytes	59, 65, 126
Motor neuron diseases: amyotrophic lateral sclerosis Charcot-Marie-Tooth disease giant axonal neuropathy hereditary spastic paraplegia myotonic dystrophy type I spinal-bulbar muscular atrophy spinal muscular atrophy spinal muscular atrophy with respiratory distress type 1	Motor neurons, astrocytes	Reduced survival Cytoplasmic and nuclear protein aggregation Altered gene expression Neurite degeneration/abnormal growth/decreased complexity Increased oxidative stress and susceptibility to stressors, including PI3K inhibition Altered subcellular axonal transport Activation of endoplasmic reticulum stress and unfolded protein response pathways C9ORF72 repeat region containing RNA foci Intrinsic membrane hyperexicitability and diminished firing capacity Noncell autonomous toxicity from disease-bearing astrocytes	34, 62, 64, 66, 67, 69, 86, 127–134
Parkinson’s disease	Dopaminergic neurons	Reduced survival Increased susceptibility to stressors Mitochondrial dysfunction Elevated disease-associated α-synuclein protein Reduced glucocerebrosidase enzymatic activity Reduced synthesis and release of dopamine Increased monoamine oxidase B expression Impaired intrinsic network activity	41, 60, 61, 94, 97