The role of DJ-1 complexes and catecholamine metabolism： relevance for familial and idiopathic Parkinson＇s disease

Autosomal recessive mutations in the PARK7 gene,which encodes for the protein DJ-1,result in a loss of function and are a cause of familial Parkinson’s disease（PD）,while increased wild-type DJ-1protein levels are associated with some forms of cancer.Several functions of DJ-1 have been described,with the greatest evidence indicating that DJ-1 is a redox-sensitive protein involved in the regulation of oxidative stress and cell survival.

Combined Effects of Family History of Cardiovascular Disease and Serum C-reactive Protein Level on the Risk of Stroke: A 9.2-year Prospective Study among Mongolians in China

Objective We aimed to evaluate the combined effect of a family history of cardiovascular disease（CVD） and high serum C‐reactive protein（CRP） on the stroke incidence in an Inner Mongolian population in China. Methods A prospective cohort study was conducted from June 2002 to July 2012, with 2,544 participants aged 20 years and over from Inner Mongolia, China. We categorized participants into four groups based on the family history of CVD and CRP levels. Results We adjusted for age; sex; smoking; drinking; hypertension; body mass index; waist circumference; and blood glucose, triglycerides, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol levels. Compared with the group with no family history of CVD/low CRP levels, the group with family history of CVD/high CRP levels had a hazard ratio（HR） of 1.78 [95% confidence interval（CI）, 1.03‐3.07; P = 0.039] of stroke, and an HR of 2.14（95% CI, 1.09‐4.20; P = 0.027） of ischemic stroke. The HRs of hemorrhagic stroke for the other three groups were not statistically significant（all P 〉 0.05）. Conclusion Participants with both a family history of CVD and high CRP levels had the highest stroke incidence, suggesting that high CRP levels may increase stroke risk, especially of ischemic stroke, among individuals with a family history of CVD.

Dyslipidemia and cardiovascular disease risk factors in patients with type 1 diabetes:A single-center experience

BACKGROUND Type 1 diabetes(T1D)contributes to altered lipid profiles and increases the risk of cardiovascular disease(CVD).Youth with T1D may have additional CVD risk factors within the first decade of diagnosis.AIM To examine risk factors for dyslipidemia in young subjects with T1D.METHODS Longitudinal and cross-sectional retrospective study of 170 young subjects with T1D(86 males;baseline mean age 12.2±5.6 years and hemoglobin A1c 8.4%±1.4%)were followed in a single tertiary diabetes center for a median duration of 15 years.Predictors for outcomes of lipid profiles at last visit(total cholesterol[TC],triglycerides[TGs],low-density lipoprotein-cholesterol[LDL-c],and highdensity lipoprotein-cholesterol[HDL-c])were analyzed by stepwise linear regression models.RESULTS At baseline,79.5%of the patients had at least one additional CVD risk factor(borderline dyslipidemia/dyslipidemia[37.5%],pre-hypertension/hypertension[27.6%],and overweight/obesity[16.5%])and 41.6%had multiple(≥2)CVD risk factors.A positive family history of at least one CVD risk factor in a first-degree relative was reported in 54.1%of the cohort.Predictors of elevated TC:family history of CVD(β[SE]=23.1[8.3],P=0.006);of elevated LDL-c:baseline diastolic blood pressure(DBP)(β[SE]=11.4[4.7],P=0.003)and family history of CVD(β[SE]=20.7[6.8],P=0.017);of elevated TGs:baseline DBP(β[SE]=23.8[9.1],P=0.010)and family history of CVD(β[SE]=31.0[13.1],P=0.020);and of low HDL-c levels:baseline DBP(β[SE]=4.8[2.1],P=0.022]).CONCLUSION Our findings suggest that elevated lipid profiles are associated with DBP and a positive family history of CVD.It is of utmost importance to prevent and control modifiable risk factors such as these,as early as childhood,given that inadequate glycemic control and elevation in blood pressure intensify the risk of dyslipidemia.

Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease

The presenilin genes(PSEN1 and PSEN2)are mainly responsible for causing early-onset familial Alzheimer’s disease,harboring~300 causative mutations,and representing~90%of all mutations associated with a very aggressive disease form.Presenilin 1 is the catalytic core of theγ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein,Notch-1,N-and E-cadherin,LRP,Syndecan,Delta,Jagged,CD44,ErbB4,and Nectin1a.Presenilin 1 plays an essential role in neural progenitor maintenance,neurogenesis,neurite outgrowth,synaptic function,neuronal function,myelination,and plasticity.Therefore,an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling,synaptic dysfunction,memory impairment,and increased Aβ42/Aβ40 ratio,contributing to neurodegeneration during the initial stages of Alzheimer’s disease pathogenesis.This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer’s disease.Furthermore,we emphasize the importance of Alzheimer’s disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer’s disease pathogenesis throughout neuronal differentiation impairment.

Analysis of the Current Status and Influencing Factors of Family Members’Collateral Stigma in Schizophrenia Patients

Objective: To investigate the associated collateral stigma of the family members of schizophrenia patients and analyze its current status and influencing factors. Methods: The Link Depreciation-Discrimination Perception Scale was used to investigate the status quo of the associated stigma of the family members of 169 schizophrenia patients diagnosed in 4 hospitals in a certain province. The results of the investigation were analyzed and summarized. Results: The detection rate of stigma associated with the family members of schizophrenia patients was 72.78%, with a score of 28.41 ± 3.92 points. The main influencing factors were the family member’s education level, the patient’s illness duration, the family member’s occupation, and the family-patient relationship. Conclusion: The detection rate of stigma associated with schizophrenia was relatively high. This requires increased attention and appropriate nursing intervention.

Genetic profiles of familial late-onset Alzheimer’s disease in China:The Shanghai FLOAD study

Compared with early-onset familial AD(FAD),the heritability of most familial lateonset Alzheimer’s disease(FLOAD)cases still remains unclear.However,there are few reported genetic profiles of FLOAD to date.In the present study,targeted sequencing of selected candidate genes was conducted for each of 90 probands with FLOAD and 101 unrelated matched normal controls among Chinese Han population.Results show a significantly lower rate of mutation in APP and PSENs,and APOE e4 genetic risk is higher for FLOAD.Among the Chinese FLOAD population,the most frequent variant was CR1 rs116806486[5.6%,95%CI(1.8%,12.5%)],followed by coding variants of TREM2(4.4%,95%CI(1.2%,10.9%))and novel mutations of ACE[3.3%,95%CI(0.7%,9.4%)].Next,we found that novel pathogenic mutations in ACE including frame-shift and nonsense mutations were in association with FLOAD regardless of APOE e4 status.Evidence from the Alzheimer’s disease Neuroimaging Initiative(ADNI)database also supported this finding in different ethnicities.Results of in vitro analysis suggest that frame-shift and nonsense mutations in ACE may be involved in LOAD through decreased ACE protein levels without affecting direct processing of APP.