Human iPSC for Therapeutic Approaches to the Nervous System: Present and Future Applications

Table 1

Neurodegenerative specific iPSC for disease modelling.

CNS disease	Genetic defect	Phenotype
Adrenoleukodystrophy [24]	ABCD1	Increased level of VLCFA in oligodendrocytes
Alzheimer’s disease [25]	Presenilin 1; Presenilin 2; APP duplication	Increased amyloid β (Aβ) secretion; Increased Aβ40 production; Increased phosphor-tau and GSK-3β activity
Amyotrophic lateral sclerosis [3]	SOD1, VAPB, and TDP43	Decreased VAPB in motor neurons; Elevated levels of TDP43 protein
Huntington’s disease [26]	CAG repeat expansion in HTT gene	Enhanced caspase activity upon growth factor deprivation
Familial dysautonomia [27]	IKBKAP	Decreased expression of genes involved in neurogenesis and neural differentiation
Parkinson’s disease [3]	LRRK2, PINK1, and SNCA	Impaired mitochondrial function in PINK1-mutated dopaminergic neurons; Increased sensitivity to oxidative stress in LRRK2 and SNCA-mutant neurons
Rett syndrome [28]	MeCP2; CDKL5	MeCP2: neuronal maturation defects, decreased synapse number; CDKL5: aberrant dendritic spines
Spinal muscular atrophy [29]	SMN1	Decreased size, number, and survival of motor neurons
Machado-Joseph disease [30]	MJD1 (ATXN3)	Excitation-induced ataxin-3 aggregation in differentiated neurons
Schizophrenia [31]	Multifactorial	Reduced neuronal connectivity, increased consumption in extramitochondrial oxygen, and elevated levels of ROS

VLCFA: very long chain fatty acid; ROS: reactive oxygen species.