Parkinson’s Disease in a Dish: What Patient Specific-Reprogrammed Somatic Cells Can Tell Us about Parkinson’s Disease, If Anything?

Table 1

Summary of studies that have used dermal fibroblasts from PD patients to model the disease.

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]
	↓; iDA	Morphological 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 𝛼-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 𝛼-syn as neurons from the unaffected relative	[16]
SNCA A53T mutation	↓; iN/iDA	Successful genetic repair of the mutation	[17]
LRRK2 G2019S; mutation	Dermal fibroblasts; ↓	Increased expression of key oxidative stress-response genes and 𝛼-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	↓; iDA	Vulnerability 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-1𝛼; 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 𝛼-syn protein levels with accumulation of 𝛼-syn, which results in neurotoxicity through aggregation dependent mechanisms	[22]

Abbreviations: 𝛼-syn: 𝛼-synuclein; DA: dopamine; iDA: induced dopaminergic neurons; iPS: induced pluripotent stem; LRRK2: Leucine-rich repeat kinase 2; PD: Parkinson’s disease; PGC-1α Peroxisome proliferator-activated receptor-𝛾 coactivator 1𝛼; SNCA: 𝛼-synuclein gene; vmDA: ventral mesencephalon dopaminergic.