Faculty Bibliography

Although synapsins are abundant synaptic vesicle proteins that are widely used as markers of presynaptic terminals, the mechanisms that target synapsins to presynaptic terminals have not been elucidated. We have addressed this question by imaging the targeting of green fluorescent protein-tagged synapsins in cultured hippocampal neurons. Whereas all synapsin isoforms targeted robustly to presynaptic terminals in wild-type neurons, synapsin Ib scarcely targeted in neurons in which all synapsins were knocked-out. Coexpression of other synapsin isoforms significantly strengthened the targeting of synapsin Ib in knock-out neurons, indicating that heterodimerization is required for synapsin Ib to target. Truncation mutagenesis revealed that synapsin Ia targets via distributed binding sites that include domains B, C, and E. Although domain A was not necessary for targeting, its presence enhanced targeting. Domain D inhibited targeting, but this inhibition was overcome by domain E. Thus, multiple intermolecular and intramolecular interactions are required for synapsins to target to presynaptic terminals

Several lines of evidence have revealed some overlapping pathologies in Alzheimer's disease (AD) and Parkinson's disease (PD). Although the alpha-2 macroglobulin gene (A2M) might be a risk factor of these two neurodegenerative diseases, conclusions from different studies have remained conflicting. Here we studied the role of A2M I1000 V polymorphism in both AD and PD in a Chinese Han population. We found that the A2M I/V genotype is associated with both AD (odds ratio (OR)=2.55, 95% confidential interval (95% CI): 1.20-5.43, attributable fraction (AF)=13.65%) and PD (OR=3.03, 95% CI: 1.30-7.02, AF=16.51%). After classifying according to the age of onset, this association is only detected in early-onset AD patients (OR=3.96, 95% CI: 1.28-12.26) and late-onset PD patients (OR=2.61, 95% CI: 0.97-7.09). Therefore, we conclude that in our samples, the A2M I/V genotype might be a susceptibility variant, even with minor effect, for both sporadic AD and PD

Several lines of evidence have suggested some common genetic risk factors for Alzheimer disease (AD) and Parkinson disease (PD) because there are some overlapping pathologies in these two neurodegenerative diseases. In the present study, we investigated the role of Apolipoprotein E gene polymorphism and the signal peptide polymorphism in alpha-1 antichymotrypsin (ACT) gene in idiopathic sporadic PD. The study was performed in a sample consisting of 68 PD cases and 160 healthy subjects in Shanghai China. We found no significant differences of ACT gene polymorphic distribution between PD cases and controls. The ApoE gene epsilon2/epsilon4 genotype was significantly more frequent in PD subjects (chi2 = 7.126, df = 1, P = 0.008) and conferred a 12.70 times susceptibility for PD (OR = 12.62, 95% CI: 1.445-110.17, chi2 = 5.259, P < 0.05, AF = 4.59%). No interaction of ApoE and ACT genes was detected in PD. Therefore, our data suggested that the ApoE epsilon2/epsilon4 genotype might be a susceptibility variant of moderate effect for sporadic idiopathic PD in our samples, whereas the ACT gene signal peptide polymorphism might not