Overexpression of Parkin Ameliorates Dopaminergic Neurodegeneration Induced by 1- Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in Mice

Abstract

Mutations in the parkin gene are currently thought to be the most common cause of recessive familial Parkinsonism. Parkin functions as an E3 ligase to regulate protein turnover, and its function in mitochondrial quality control has been reported recently. Overexpression of parkin has been found to prevent neuronal degeneration under various conditions both in vivo and in vitro. Here, we generated a transgenic mouse model in which expression of wild type parkin was driven by neuron-specific enolase (NSE) promoter. We reported that both young and old parkin transgenic mice exhibited less reduction of striatal TH protein and number of TH positive neurons in the substantia nigra induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP), compared to wild type littermates. MPTP-induced mitochondrial impairment in the substantia nigra was improved in young parkin transgenic mice. Decreased striatal α-synuclein was demonstrated in old parkin transgenic mice. These results provide reliable evidence from the transgenic mouse model for parkin that overexpression of parkin may attenuate dopaminergic neurodegeneration induced by MPTP through protection of mitochondria and reduction of α-synuclein in the nigrostriatal pathway.

Cinnamon Treatment Upregulates Neuroprotective Proteins Parkin and DJ-1 and Protects Dopaminergic Neurons in a Mouse Model of Parkinson’s Disease

“…Parkin and DJ-1 are known to stimulate and support the survival of existing dopaminergic neurons. Consistently, in PD, Parkin and DJ-1 have been suggested as rescuers of these vulnerable cells (Zhou and Freed 2005; Ng et al 2009; Bian et al 2013). However, clinical application of these molecules in PD has been limited because of difficulties in delivery.…”

Parkin and PINK1 functions in oxidative stress and neurodegeneration

“…Parkin overexpression also has been shown to protect against nigral dopamine neuron loss in animal models of PD (Lo Bianco et al 2004; Vercammen et al 2006; Ulusoy and Kirik 2008; Bian et al 2012). Parkin gene expression is upregulated under cellular stress, and transcription factors such as ATF4 and p53 can increase Parkin expression, whereas c-Jun and N-myc act as transcriptional repressors of Parkin (West et al 2004; Bouman et al 2011; Zhang et al 2011).…”

NRSF is an essential mediator for the neuroprotection of trichostatin A in the MPTP mouse model of Parkinson's disease

“…HPLC was performed based on the previous study (Bian et al, 2012). The dissected left striatum was homogenized in 0.4 M HClO 4 at 4 0 C and then centrifuged at 10,000 rpm for 10 min (4 0 C).…”