In conclusion, the suppression of nNOS enzyme by targeted siRNAs modified the progressive death of dopaminergic cells induced by 6-OHDA and merits further pre-clinical investigations as a neuroprotective approach for PD.
Moreover, inhibition of two NO-synthesizing enzymes, neuronal NOS (nNOS) and inducible NOS (iNOS), displays neuroprotective effects in the MPTP model of Parkinson's disease (PD).
Quantitation of SS mRNA expression on emulsion dipped sections revealed a significant increase (82%) in the MML of the globus pallidus in PD (56.5 microm2 of silver grain/cell, n = 9 cases) compared to controls (26.3 microm2/cell, n = 13 cases, p < 0.01, Student's t-test), paralleling the increase previously observed by this group for NOS mRNA.
The analysis results indicated that NOS1 exon18 polymorphism was associated with developing PD in 4 genetic models (allelic: OR = 1.25, 95%CI 1.09-1.44, P = 0.001; homozygous: OR = 1.79, 95%CI 1.32-2.45, P < 0.001; recessive: OR = 1.70, 95%CI 1.26-2.28, P < 0.001; dominant: OR = 1.22, 95%CI 1.02-1.46, P = 0.03), whereas exon29 polymorphism was not correlated to PD susceptibility.
The polymorphism's length has been suggested to affect NOS1 transcription and play a role in Parkinson's disease (PD); however, the actual influence of the polymorphism on NOS1 transcription has not been studied.
These data implicate NOS1 and NOS2A as genetic risk factors for PD and demonstrate that their interactions with established environmental factors may modulate the environmental effects.
This review mainly focuses on the NOS genes - their differential regulation and genetic heterogeneity, highlighting their significance in the pathobiology of PD.
To determine if NOS gene polymorphism affects the 5' flanking region that is immediately upstream of the transcription start site lying between the TATA element and CAATT boxes in PD, and differs significantly between patients with PD and normal controls, we studied genetic polymorphism in that region of the neuronal NOS gene in Chinese patients with PD living in Taiwan.
While nNOS exon 29 TT variant genotype [odds ratio (OR) = 2.20, 95 % CI = 1.08-5.34, P = 0.040], combined TT and CT variants [OR = 1.68, 95 % CI = 1.05-2.69, P = 0.031] and T allele [OR = 1.58, 95 % CI = 1.10-2.28, P = 0.014] were found to be significantly associated with PD susceptibility, no association between nNOS exon 18 [OR for TT carriers = 1.97, 95 % CI = 0.89-4.20, P = 0.09 and OR for T allele = 1.35, 95 % CI = 0.94-1.93, P = 0.098] and PD risk was observed.