A short overview on the role of α-synuclein and proteasome in experimental models of Parkinson’s disease

Adenosine A2A receptor gene disruption protects in an α‐synuclein model of Parkinson's disease

“…12 Similar uncertainty exists over the mechanisms by which human α-SYN mutations or overexpression can produce neurodegeneration in PD and its models. However, consistent with evidence that α-synuclein toxicity may be mediated by proteosomal (ubiquitin system) dysfunction, 14 the ubiquitin proteosomal system (UPS) is impaired in aged transgenic mutant hm 2 -αSYN mice like those studied here, compared to their transgenic WT hw-αSYN and non-transgenic controls. 15 Whether the prevention of cell loss observed in A 2A KO mice is due to attenuation of UPS dysfunction or downstream mediator of α-synuclein toxicity remains to be clarified.…”

Loss of spinal motor neurons and alteration of alpha-synuclein immunostaining in MPTP induced Parkinsonism in mice

“…Again asyn immunostaining increases in the cytosol, after a chronic MPTP infusion (Fornai et al, 2005;Meredith et al, 2008). The increase of a-syn in the neurons could induce the formation of toxic a-syn oligomers (Stefanis et al, 2001;Tanaka et al, 2001;Bucciantini et al, 2002;Walsh et al, 2002;Giorgi et al, 2006), thus leading to neuronal toxicity.…”

Protein Carbonyl and the Methionine Sulfoxide Reductase System

“…For example, mutations in two enzymes of the ubiquitin system, parkin and UCH-L1, have been identified as causative genetic defects for certain familial forms of PD (11). Although UCH-L1 has been implicated in a rare familial form of PD (26), little is currently known about the role of UCH-L1 in the sporadic forms of PD. With a proteomics approach, UCH-L1 was shown to be significantly oxidized in both PD and AD brains by the addition of carbonyls (18).…”