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Table 1 Neurological and psychiatric diseases where iPS cells have been derived from affected individuals

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)

  1. ND, not demonstrated; FMR1, fragile × mental retardation 1; HPRT1, hypoxanthine phosphoribosyltransferase 1; IGF1, insulin-like growth factor 1; IKBKAP, inhibitor of kappa light polypeptide gene enhancer in B cells, kinase complex-associated protein; iPS, induced pluripotent stem; LRRK2, leucinerich repeat kinase 2; MECP2, methyl CpG binding protein 2; PINK1, PTEN-induced putative kinase 1; SMA, spinal muscular atrophy; SMN, survival of motor neuron; SOD1, superoxide dismutase 1.