Table 1 Summary of the pathogenic characteristics observed in PD animal models

Drug-induced parkinsonism

Reserpine

Rodents

Yes

(SNpc and

Striatum)

Yes

Yes

NR

NR

NR

Oxidative stress

Non-motor phenotype

Transient loss of DA neurons

Sexual dimorphic effect

Haloperidol

Rodents,

primates

Yes

(Striatum)

Yes

No

Yes

NR

Yes

Crosses the BBB

Induces features of neuroinflammation

No loss of SNpc DA neurons

Neurotoxic animal models

6-OHDA

C. elegans*,

rodents,

primates

Yes

(SNpc and

Striatum)

Yes

No

Yes

Yes

Yes

Oxidative stress

Non-motor phenotype

Does not cross the BBB

MPTP

Rodents and

primates

Yes

(SNpc and

Striatum)

Yes

Yes

Yes

Yes

Yes

Oxidative stress

Recreates phases of PD

Non-motor phenotype

Phenotype variability in rodents

LPS

Rodents

Yes

(SNpc and

Striatum)

Yes

Yes

Yes

Yes

Yes

Oxidative stress

Non-motor phenotype

No α-syn inclusions

Tau pathology

Agrochemical-induced animal models

Rotenone

C. elegans*,

Drosophila*

and rodents

Yes

(SNpc and

Striatum)

Yes

Yes

Yes

Yes

Yes

Oxidative stress

Non-motor phenotype

Inter-individual variability

Paraquat & Maneb

C. elegans*,

Drosophila*

and rodents

Yes

(SNpc)

Yes

Yes

Yes

NR

Yes

Combination increases toxicity

Oxidative stress

Non-motor phenotype

Intact striatal fibers in rats

Induces pulmonary fibrosis

Transgenic models

PRKN & PINK1

C. elegans* (KO)

Yes

Yes

N/A

Yes

NR

NR

Lifespan decreases

Drosophila*

(KO)

Yes

Yes

N/A

Yes

NR

NR

Degeneration of flight muscles

No DA cell loss in PRKN ortholog-KO Drosophila

Mice

(KO)

Yes

(SNpc and striatum)

Yes

No

Yes

No

Yes

Mitochondrial dysfunction

Slow degeneration

Primates (KO)

Yes

(SNpc)

Yes

NR

NR

NR

NR

Years to develop the phenotype

LRRK2

C. elegans*

(OE)

Yes

Yes

N/A

Yes

Yes

NR

Progressive loss of DA neurons

Drosophila*

(OE)

Yes

Yes

N/A

Yes

Yes

NR

Synaptic alterations

Tau pathology

Mice

(OE)

Yes

(SNpc and Striatum)

Yes

Yes

Yes

Yes

Yes

Oxidative stress

Synaptic alterations

Tau pathology

DJ-1

Mice

(KO)

Yes

(SNpc and Striatum)

Yes

No

Yes

Yes

NR

May target early phases of pathology

Age-dependent phenotype

UCH-L1

Drosophila*

(KO)

Yes

Yes

N/A

NR

NR

NR

Progressive age-dependent loss of SNpc DA neurons

Mice

(OE)

Yes

(SNpc and Striatum)

Yes

No

NR

NR

NR

Increased vulnerability to α-syn

Not well characterized

GBA1

Drosophila*

(KO/KI)

Yes

Yes

N/A

NR

NR

NR

Increases aggregation in mutant α-syn model

Mice

(KI)

Yes

Yes

Yes

Yes

Yes

Yes

Cognitive deficits

No α-syn aggregates in GBA1 L444P heterozygous mice

Lmx1a/b

Mice

(KO)

Yes

(SNpc and Striatum)

Yes

Yes

Yes

Yes

NR

Altered development

KO needs to be performed on mature animals

Otx2

Mice

(KO)

Yes

(SNpc and Striatum)

Yes

N/A

N/A

N/A

N/A

Loss of DA neurons in the VTA

Altered development

KO needs to be performed on mature animals

Foxa1/2

Mice

(KO)

Yes

(SNpc and Striatum)

Yes

No

N/A

N/A

N/A

Altered development

KO needs to be performed on mature animals

Pitx3

Mice

(KO)

Yes

(SNpc and Striatum)

Yes

N/A

N/A

N/A

N/A

Altered development

KO needs to be performed on mature animals

Nurr1 & En1

Mice

(KD)

Yes

(SNpc and Striatum)

Yes

N/A

N/A

N/A

N/A

Total depletion is not viable

(Altered development)

KD needs to be performed on mature animals

c-Rel

Mice

(KO)

Yes

(SNpc and Striatum)

Yes

N/A

N/A

N/A

N/A

Altered development

KO needs to be performed on mature animals

Mitochondrial impairment

Mice

(POLG)

No

No

NR

Yes

NR

NR

No phenotypic accentuation in DJ-1/PRKN deficient mice

Mice

(Ndufs2 KO)

Yes

(Striatum)

Yes

NR

Yes

NR

NR

Total reduction of MCI activity

Mouse death at 5–6 months

Mice

(Ndufs4 KO)

Yes

(Striatum)

No

Yes

Yes

NR

NR

Partial reduction of MCI activity

No loss in SNpc

α-syn models

WT α-syn

Mice

(M61)

Yes

(Striatum)

Yes

Yes

Yes

NR

Yes

No degeneration of SNpc DA neurons

C. elegans* and

Drosophila*

Yes

Yes

Yes

Yes

NR

NR

No endogenous α-syn

C-terminally truncated α-syn

Mice

(MI2)

Yes

(SNpc and Striatum)

Yes

Yes

NR

NR

NR

Null endogenous α-syn background

α-syn expression restricted to

DA neurons

E46K human α-syn

Mice

(M47 line)

NR

Yes

Yes

NR

NR

Yes

No α-syn in SNpc DA neurons

A30P human α-syn

Mice

NR

Yes

Yes

Yes

Yes

NR

Around a year to develop strong phenotype

No degeneration of SNpc DA neurons

C. elegans* and

Drosophila*

Yes

Yes

Yes

Yes

NR

NR

Lower α -syn accumulation than α-syn WT

Lower α -syn accumulation than α-synA53T

A53T human α-syn

Mice

(M83 line)

NR

Yes

Yes

Yes

Yes

Yes

α-syn inclusions in non-PD-related areas

C. elegans* and

Drosophila*

Yes

Yes

Yes

Yes

NR

NR

No endogenous α-syn

PFFs

Mice

Yes

Yes

Yes

NR

NR

Yes

Slow phenotype development in WT mice (6 months)

Accelerated phenotype in A53T transgenic mice

Primates

Yes

NR

Yes

NR

NR

NR

-

Viral-vector-mediated models

α-synuclein viral expression

Rodents and

primates

Yes

(SNpc and

Striatum)

Yes

Yes

Yes

Yes

Yes

Progressive neuronal loss

Non-motor phenotype

Variable phenotype depending on the injection

Non-physiological α-syn expression

NM-like production

Rodents

Yes

(SNpc and

Striatum)

Yes

Yes

Yes

Yes

Yes

Age-dependent progression