Impaired proteostasis | DA neurons degeneration | Treatment | References |
---|---|---|---|
Intracellular deposit of in α‐synuclein observed in 30% of DA neurons | Approx. 30 (25–35%) % of cell loss (TH positive cells) in SNpc | C57BL/6 mice treated with Paraquat once a week for 3 weeks at 10 mg/kg i.p. |
Manning –Bog et al. (2003) Fernagut (2007) |
Increase of approx. 91% of α‐synuclein inclusion (proteinase‐K‐resistant α‐syn aggregates) only observed in α‐synuclein overexpressing animals | Approx. 25% loss of DA neurons (stereological analysis TH‐positive neurons) in both WT as well as α‐synuclein overexpressing animals | Weekly i.p. administration of 10 mg/kg paraquat for 3 weeks in mice WT and overexpressing α‐synuclein | |
Approx. 50% reduction in α‐synuclein expression in SN | Approx. 40% loss of DA neurons (TH+ and FOX3 + neurons) | Paraquat 10 mg/kg i.p. twice a week for 4 weeks to adult Swiss albino mice | Mitra et al. (2011) |
Approx. 50% increase of α‐synuclein expression (immunoreactivity and protein) | Paraquat significantly reduced PQ‐elicited dopaminergic neuronal loss from 37% | Wistar rat receiving four i.p. injections, separated by 1 day, of paraquat at 10 mg/kg per day | Cristovao et al. (2012) |
Proteasome inhibition (approx. 60% at 24 h and 80% at 48 h) Increased protein levels of α‐synuclein (2.3‐fold at 24 h and 3‐fold at 48 h) Increased ubiquinated protein levels (1.5‐fold at 24 h and 1.7‐fold at 48 h) |
Reduction of 60% in cell viability at 48 h | DA SH‐SY5Y cells treated with paraquat 0.5 mM | Yang et al. (2007) |
Accumulation of AV (%vacuolated cell volume) at 6, 15 and 24 h was 20, 40 and 45% respectively. Inhibition of PQ‐induced autophagic vacuolisation and protein degradation after treatment with 3‐MA |
25% of nuclear apoptosis at 24 h (caspase‐3 maximum level) Apoptosis cell death was accelerated and caspase‐3 activation increased after 3‐MA treatment |
DA SH‐SY5Y cells treated with paraquat 10 μM DA SH‐SY5Y cells treated with paraquat 10 μM were then treated with prototypic autophagy inhibitor 3‐MA 10 mM |
Gonzalez‐Polo et al. (2007) |
SiRNA knockdown of DJ‐1 has no effect alone on the formation of autophagic vacuoles. In the presence of PQ (250 μM), DJ‐1 knockdown significantly inhibited cytoplasmic accumulation of autophagic vacuoles, with an additive increase in apoptotic chromatin condensation |
SiRNA knockdown of DJ‐1 induces apoptotic death (25–30%) The combination of DJ‐1 si RNA and Paraquat induces additive apoptotic death (more significant in the range 250–500 μM PQ) and caspase‐3 activation. Apoptosis cell death was accelerated after 3‐MA treatment |
DA SH‐SY5Y cells transfected with DJ‐1 si RNAs and exposed to paraquat 250–500 μM DA SH‐SY5Y cells transfected with DJ‐1 si RNAs exposed to paraquat 250–500 μM treated with prototypic autophagy inhibitor 3‐MA 10 mM |
Gonzalez‐Polo et al. (2009) |
Increased expression of ER stress proteins and inhibition proteosomal activity (60–70% reduction at 500 μM) | Time and concentration‐dependent cell death (70% with 500 μM of PQ for 48 h) reduction in cell survival | Rat N27 mesencephalic dopaminergic cells treated with Paraquat (100–500 μM) for 12–48 h | Chinta et al. (2010) |
Increased 133% of α‐synuclein Increased by 13% (not statistically significant) in 19S proteasome function and decrease of 5% 20S proteasome function (not stat signif) Increase by 43% in mTOR (autophagy inhib) Increase 81% beclin‐1 (autophagy inducer) Increased in Atg 12 of 36% Decrease of appr 24% in LC3 II to LC3 I ratio |
C57BL/6 mice treated with Paraquat twice a week for 6 weeks at 10 mg/kg i.p. (12 doses) | Wills et al. (2012) | |
Increase 115% α‐synuclein in striatum 10% decrease in 19S proteasome function and 5% in 20S proteasome function (both not statist significant) Increase 47% in mTOR and stat sig in beclin‐1(81–95%) Increase in Atg12 (40%) LC3 II to LC3 I ratio decreased up to 25% |
TH neuronal loss 43% | C57BL/6NC mice treated with Paraquat twice a week for 4 weeks at 10 mg/kg i.p. | Su et al. (2015) |