Background:Dopamine transporter based imaging has high diagnostic performance in distinguishing patients with Parkinson’s disease(PD)from patients with non-Parkinsonian syndromes.Our previous study indicated that the“Sniffin’Sticks”odor identification test(SS-16)acts as a valid instrument for olfactory assessment in Chinese PD patients.The aim of the study was to compare the efficacy of the two methods in diagnosing PD.Methods:Fifty-two PD patients were involved in this study and underwent single photon emission computed tomography(SPECT)imaging using the labeled dopamine transporter radiotracer ^(99)mTc-TRODAT-1 to assess nigrostriatal dopaminergic function.Olfactory function was assessed with the“Sniffin’Sticks”odor identification test(SS-16)in all patients who received DAT-SPECT scanning.Statistical analysis(SPSS version 21)was carried out to determine the diagnostic accuracy of SS-16 as well as its correlation with ^(99)mTc-TRODAT-1 SPECT,its positive predictive value(PPV),and negative predictive value(NPV).Results:We identified a negative correlation between SS-16 and DAT SPECT(Kappa=0.269,p=0.004).By using the ^(99)mTc-TRODAT-1 uptake results as the gold standard,the sensitivity and specificity of SS-16 was 56.8 and 37.5%,respectively.Furthermore,the negative and positive predictive values were calculated as 13.6 and 83.3%,respectively.Conclusions:SS-16 would not be used as a diagnostic tool for early stage PD patients.Negative results of SS-16 would not exclude the diagnosis of PD.Further tests are needed for validation.
Wenyan KangFangyi DongDunhui LiThomas J.QuinnShengdi ChenJun Liu
Parkinson＇s disease （PD） is pathologically characterized by the presence of α-synuclein （α-syn）-positive intra-cytoplasmic inclusions named Lewy bodies in the dopaminergic neurons of the substantia nigra. A series of morbid consequences are caused by pathologically high amounts or mutant forms of α-syn, such as defects of membrane trafficking and lipid metabolism. In this review, we consider evidence that both point mutation and overexpression of α-syn result in aberrant degradation in neurons and microglia, and this is associated with the autophagy-lysosome pathway and endosome-lysosome system, leading directly to pathological intracellular aggregation, abnormal externalization and re-internalization cycling （and, in turn, internalization and re-externalization）, and exocytosis. Based on these pathological changes, an increasing number of researchers have focused on these new therapeutic targets, aiming at alleviating the pathological accumulation of α-syn and re-establishing normal degradation.
The growth factor receptor-bound protein 2 （Grb2） -associated binder （Gab） proteins are intracellular scaffolding/ docking molecules,and participate in multiple signaling pathways,usually acting as the downstream effector of protein-tyrosine kinases （PTKs） -triggered signal transduction pathway.When phosphorylated by PTKs,Gab proteins can recruit several signaling molecules （p85,SHP2,and Crk） ,and subsequently activate multiple transmitting signals that are critical for cell growth,survival,differentiation and apoptosis.Recently,it has been reported that Gab2 polymorphism is associated with the increase in the risk of Alzheimer’s disease （AD） and is involved in the pathogenesis of AD.This review mainly focuses on the structure and function of Gab2 protein and its role in the pathogenesis of AD.
SK channels are small conductance calcium-activated potassium channels that are widely expressed in different neurons with distinct subtypes.They play an important role in modulating synaptic plasticity,dopaminergic neurotransmission, and learning and memory.The present review was mainly focused on the recent findings on the contradictory roles of SK channels in modulating dopaminergic neurons in substantia nigra and in the pathogenesis of Parkinson＇s disease （PD） . Besides,whether modulation of SK channels could be a potential target for PD treatment was also discussed.
