Table 4 Different animal models and their applications in PD research. LB-Lewy bodies, IFC-impaired fear conditioning, CD-cognitive deficits, MD-mitochondrial, deficits, RA-reduced anxiety, ASP-affected synaptic plasticity, RD-reduced dopamine level
Category | Models | Mechanism | NS loss | Inclusions | Motor deficit | Non-motor deficit | Applications | Demerits | Refs. | ||
Environ mental toxins | 6-OHDA | Complex I inhibition | +++ | _ | +++ | Cognitive, psychiatric, and GI disorders | Screen therapies for PD, study mechanisms of cell death | Degeneration non-progressive | [283] | ||
MPTP | Complex I inhibition | ++ | -, presence of SNCA at SNpc | +++ | Numerous | Screen therapies for PD, study mechanisms of cell death | Non-progressive rare inclusions | ||||
Rotenone | Complex I inhibition, ↑ROS | ++ | Presence of SNCA at SNpc | +++ | Decrease GI motility | Test neuroprotective compounds | morbidity, mortality, time consuming & laborious | [286] | |||
Paraquat | Complex I inhibition, ↑ROS | +++ | No inclusions at SNpc | _ | Not detected | Test neuroprotective compounds | Substantial morbidity, mortality, time consuming & laborious | ||||
Maneb | Impairment of glutamate and DA uptake | + | _ | + | Not detected | Study glutamate uptake in DA neurons | No inclusion, less DA neuronal damage | ||||
Others | SHH, Nurr1, Pitx3, EN1 | Impaired protein synthesis in DA-neurons | ++ | _ | +/− | Not known | Study the mechanism of Translation in DA neurons | No SNCA | |||
MitoPark | Mitochondrial deficit | ++ | +/− | + | Not known | Study the role of mitochondria in PD | Less motor deficit | ||||
PDC | EAATs blockade, excitotoxicity, ↑ROS | ++ | _ | + | Not known | To study excitotoxicity and Oxidative pathway in PD | No SNCA | ||||
Genetic | Parkin (PARK2) | Loss of ubiquitin E3- ligase activity | +/− | +/− | +/− | _ | Study the role of E3 ligase in PD | No inclusion, less DA neuronal damage | |||
LRRK2 (PARK 8) | Loss of enzymatic activity | _ | _ | Drosophila + | Not detected | Study the role of LRRK2 mutations related to PD | No SNCA nor no DA degeneration | ||||
PINK (PARK6) | Mitochondrial damage | +/− | +/− | +/− | Not detected | Study the role of mitochondria in PD | No SNCA or no DA degeneration | ||||
DJ-1(PARK 7) | Increase ROS, Mito. dysfunction | +/− | +/− | +/− | Not detected | Study oxidative stress & mitochondrial dysfunction in PD | Less inclusion & DA neuronal damage | ||||
SNAC mutation and animal models of PD | |||||||||||
Models | Promoter | Background | SNCA | Motor signs | Nonmotor signs | TH neurons loss | Disease progression | Ref | |||
WT, A53T | PDGF-b | C57BL/6 9 DBA2 | + | + | – | + | – | ||||
A53T | Mouse Thy-1 | C57BL/6 | LB | + | – | – | – | [305] | |||
WT, A30P, A53T | Mouse Thy-1 | C57BL/6 | + | + | + | – | + | ||||
WT, (A30P) | Mouse Thy-1 | C57BL/6 x DBA2 | + | + | IFC | + | + | ||||
Y39C | Mouse Thy-1 | FVB/N | + | + | CD | – | + | [309] | |||
A30P + A53T | Human Thy-1 | C57BL/6 x DBA2 | + | + | – | + | + | [310] | |||
(WT), (A30P), A53T | Mouse prion | C3H/HeJ 9 C57BL/6 J backcrossed into C57BL/6 J PARKIN KO | + | + | MD | – | + | ||||
WT, A53T | Mouse prion | C57BL/6 x C3H | + | + | RA | – | + | ||||
(WT), A53T | Mouse prion | FVB/N, FVB 9129, SNCA-KO | – | + | – | – | + | [315] | |||
(WT), A30P | Mouse prion | C57BL/6 J 9 DBA2 backcrossed into C57BL/6 J | – | + | ASP | – | – | [316] | |||
WT, A30P, A53T | Hamster prion | C57BL/6 J x SJL | – | + | – | – | + | ||||
WT, A30P, A53T | Rat THP | Swiss Webster x C57BL/DBA | – | – | – | – | – | [287] | |||
WT, A30P ± A53T | Rat THP | C57BL/6 | – | + | – | – | + | [319] | |||
WT, A30P, A53T | CaM-tTA (tet-off) | C57BL/6 (WT and A30P), C57BL/CH3 (WT and A53T) | – | + | CD | – | + | ||||
A30P | KI in endogenous SNCA | C57BL/6 | – | + | – | RD | + | [322] | |||
WT, A30P, A53T | Endogenous SNCA (BAC) | FVB/N 9129S6 / SvEvTac | – | + | + | – | + | [323] | |||