Here, we report that oxidatively-mediated reductions in parkin solubility and function in a mouse model of age-related sporadic PD coincides with increased PARIS levels and reduced PGC-1α signaling.
These findings indicate that TKT might be a SN-specific target of PARIS, providing new clues to understand the mechanism underlying selective DNs death in PD.
Although ZNF746, also known as Parkin-interacting substrate (PARIS), has been reported to suppress peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and its target gene NRF-1 leading to the neurodegeneration in Parkinson's disease, its function in tumorigenesis has yet to be investigated.
Thus, suppression of parkin interacting substrate protein could be a potential therapeutic strategy to halt the progression of Parkinson's disease and related α-synucleinopathies.
We found that 9 of the 17 reported novel PD risk loci showed very similar effects in Europeans and East Asians (I<sup>2</sup> = 0 to 10.7%), of which 2 loci ITPKB and ZNF184 were significantly associated with PD in our samples.
Therefore, we performed a replication study of 5 of the most commonly identified candidate variants, including SORBS3 rs2280104, SCN3A rs353116, TOX3 rs4784227, GLAC rs8005172, and ZNF184rs9468199, in a large sample of patients with PD (1506) and multiple system atrophy (MSA, 496) in a Chinese population.
Sequestosomal protein p62/A170/ZIP, which is an oxidative stress-related protein and a ubiquitin-binding protein, is a component protein of Lewy bodies that are observed in patients with Parkinson's disease.
We have tested 3 novel dual receptor agonists DA-JC1, DA-JC4 and DA-CH5 in comparison with the GLP-1 analogue liraglutide (all drugs at 25 nmol/kg ip once-daily for 6 days) in the MPTP mouse model of PD (4 × 25 mg/kg ip).
The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease.
Previous research has demonstrated that GLP-1 analogs are neuroprotective in several neurological disease models including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke.