Synaptic dysfunction: Studies in a number of the PARK2 knockout lines suggest the presynaptic dopamine transmission is perturbed. In the Park2tm1Shn knockout line, the evoked dopamine signal of neurons was reduced and could not be restored with DAT inhibition (Goldberg et al., 2003). The normal function of Parkin in dopaminergic synaptic transmission is been explored and found that the signal is lower in parkin-/- mice relative to the control, indicating that loss of Parkin indeed decreased DA release. Parkin plays a crucial role in the nigrostriatal circuit that is found to be affected in PD. Physiological analysis for the nigrostriatal circuit in parkin-/-mice point towards a marked impairment in striatal synaptic plasticity(Tohru Kitada et al., 2009).
Our physiological analysis for the nigrostriatal circuit in parkin)/) mice indicated a marked impairment in striatal synaptic plasticity.
Our physiological analysis for the nigrostriatal circuit in parkin)/) mice indicated a marked …show more content…
Parkin is usually overexpressed in response to unfolded protein stress and shown to alleviate ER stress by protecting the cell from apoptosis via its E3 activity (Imai, Soda, & Takahashi, 2000). Parkin mediates the formation of a lysine-48 polyubiquitin chain linked to the target protein, which functions as a signal for degradation by the proteasome thus it maintains the turnover of misfolded and short-lived intracellular proteins (Chew et al., 2011).The ubiquitin-ligase Park2, once it is activated, rapidly catalyzes the ubiquitination of a vast array of mitochondrial proteins and many other substrates(Veeriah, Morris, Solit, & Chan, 2010) [, 92, 93]. Mutational loss of E3 activity of parkin, therefore, causes accumulation of a vast array of mitochondrial proteins and many other substrates and finally induce ER stress-mediated cell death (Imai et al.,
Our physiological analysis for the nigrostriatal circuit in parkin)/) mice indicated a marked impairment in striatal synaptic plasticity.
Our physiological analysis for the nigrostriatal circuit in parkin)/) mice indicated a marked …show more content…
Parkin is usually overexpressed in response to unfolded protein stress and shown to alleviate ER stress by protecting the cell from apoptosis via its E3 activity (Imai, Soda, & Takahashi, 2000). Parkin mediates the formation of a lysine-48 polyubiquitin chain linked to the target protein, which functions as a signal for degradation by the proteasome thus it maintains the turnover of misfolded and short-lived intracellular proteins (Chew et al., 2011).The ubiquitin-ligase Park2, once it is activated, rapidly catalyzes the ubiquitination of a vast array of mitochondrial proteins and many other substrates(Veeriah, Morris, Solit, & Chan, 2010) [, 92, 93]. Mutational loss of E3 activity of parkin, therefore, causes accumulation of a vast array of mitochondrial proteins and many other substrates and finally induce ER stress-mediated cell death (Imai et al.,