Forms of PD Source of cells Main findings References Sporadic Dermal fibroblasts ↓ PD-specific iPS cells are able to generate dopaminergic neurons [11 ] iPSC New human iPS cell differentiation protocol to produce vmDA neuron [12 ] ↓ iDAMorphological alterations (reduced numbers of neuritis and neurite arborization), accumulation of autophagic vacuoles [13 ] Dermal fibroblasts ↓ iDA Rapid and efficient induction of iDA from human PD patient fibroblasts [14 ] Familial SNCA triplication Dermal fibroblasts ↓ Accumulation of
-syn, inherent overexpression of markers of oxidative stress, and sensitivity to peroxide induced oxidative stress [15 ] SNCA triplication iPSC Production of double the amount of
-syn as neurons from the unaffected relative [16 ] SNCA A53T mutation ↓ iN/iDASuccessful genetic repair of the mutation [17 ] LRRK2 G2019S mutation Dermal fibroblasts ↓ Increased expression of key oxidative stress-response genes and
-syn protein. Increased sensitivity to caspase-3 activation and cell death caused by exposure to stress agents [18 ] LRRK2 G2019S mutation iPSC Morphological alterations (reduced numbers of neurites and neurite arborization), accumulation of autophagic vacuoles [13 ] LRRK2 G2019S, R1441C mutations ↓ iDAVulnerability associated with mitochondrial dysfunction which could be rescued with coenzyme Q10, rapamycin, and the LRRK2 inhibitor GW5074 [19 ] Parkin mutation Increased transcription of monoamine oxidases and oxidative stress, reduced DA uptake and increased spontaneous DA release [20 ] PINK1 mutation Dermal fibroblasts ↓ iPSC iDA Impaired recruitment to lentivirally expressed parkin to mitochondria, increased mitochondria copy number, upregulation of PGC-1
; corrected by lentiviral expression of wild-type PINK1 [21 ] PINK1 Q456X mutation Vulnerability associated with mitochondrial dysfunction which could be rescued with coenzyme Q10, rapamycin, and the LRRK2 inhibitor GW5074 [19 ] Risk gene Glucocerebrosidase Dermal fibroblasts ↓ iPSC ↓ iDA Dramatic increase in
-syn protein levels with accumulation of
-syn, which results in neurotoxicity through aggregation dependent mechanisms [22 ]