From: Induced pluripotent stem cells in the study of neurological diseases
Disease | Reference | Molecular defect | Phenotype of iPS-derived cells | Therapeutic response (compound) |
---|---|---|---|---|
Down syndrome | Park and colleagues [48] | Trisomy 21 | ND | ND |
Lesch-Nyhan syndrome (carrier state) | Park and colleagues [48] | Heterozygous point mutations in HPRT1 gene | ND | ND |
 | Khan and colleagues [55] |  |  |  |
Huntington disease | Park and colleagues [48] | Trinucleotide expansion in HUNTINGTIN | ND | ND |
 | Zhang and colleagues [50] |  | Enhanced caspase 3/7 activity after growth factor withdrawal | ND |
Duchenne and Becker muscular dystrophy | Park and colleagues [48] | Mutations in DYSTROPHIN | ND | ND |
 | Kazuki and colleagues [49] |  |  |  |
Familial amyotrophic lateral sclerosis | Dimos and colleagues [13] | Mutations in SOD1 gene | ND | ND |
 | Boulting and colleagues [34] |  |  |  |
Spinal muscular atrophy | Ebert and colleagues [14] | Mutations in SMN1 gene | Reduced size and number of motor neurons, reduced SMN protein in iPS cells | Increased SMN gem number in SMA iPS cells (valproic acid, tobramycin) |
Familial dysautonomia | Lee and colleagues [29] | Partial skipping of exon 20 of IKBKAP, reduced IKAP protein | Decreased expression of genes involved in neurogenesis and neuronal differentiation; defect in neural crest migration | Increase in the percentage of differentiating neurons and in the expression of peripheral neuron markers (kinetin) |
Fragile × syndrome | Urbach and colleagues [56] | Trinucleotide (CGG) expansion, silencing of FMR1 | ND | ND |
Angelman syndrome and Prader-Willi syndrome | Chamberlain and colleagues [51] | Chromosome 15q deletion (imprinting disorders) | ND | ND |
 | Yang and colleagues [52] |  |  |  |
Parkinson disease | Park and colleagues [48] | Unknown (sporadic) | ND | ND |
 | Soldner and colleagues [16] |  |  |  |
 | Swistowski and colleagues |  |  |  |
 | [17] |  |  |  |
 | Hargus and colleagues [37] |  |  |  |
 | Nguyen and colleagues [38] | Mutations in LRRK2 | Increased expression of stress-response genes, increased α-SYNUCLEIN levels and oversensitivity to stress agents by dopaminergic neurons | ND |
 | Seibler and colleagues [42] | Mutations in PINK1 | Impaired recruitment of Parkin to mitochondria, increased mitochondrial copy number, upregulation of PGC-1α in dopaminergic neurons | Phenotype corrected by expression of wildtype PINK1 |
Rett syndrome | Hotta and colleagues [57] | Mutation in MECP2 | Decreased synapse number, reduced spines, increased LINE1 retrotransposon mobility | Increase in glutamatergic synapse number (IGF1); increase in MeCP2 protein increase in MeCP2 protein levels and glutamatergic synapse numbers (gentamicin) |
 | Marchetto and colleagues [15] |  |  |  |
 | Muotri and colleagues [33] |  |  |  |
Schizophrenia | Brennand and colleagues [47] | Unknown | Reduced neurite density, neuronal connectivity and glutamate receptor expression; altered gene expression of components of the cyclic AMP and WNT signaling pathways | Increase in neuronal connectivity and glutamate receptor expression (loxapine) |