Background: Mutations in the glucocerebrosidase (GBA) gene have recently been identified as contributing to the development of Parkinson disease (PD) in Ashkenazi Jews. Methods: To investigate whether this finding can be confirmed in a Taiwanese population, we conducted a case control study in a cohort of 518 PD patients and 339 controls for the three common GBA mutations in Taiwan, L444P, RecNciI and R120W, using PCR restriction enzyme assay and DNA sequencing. Results: Heterozygous GBA mutations were detected in 16 PD patients (3.1%) and four controls (1.2%). Although this difference was not statistically significant (p = 0.0703), the average age at disease onset of the 16 PD patients (50.6 (12.3) years) was significantly younger than that of the total patient group (63.8 (10.5) years; p = 0.0007) and the non-carrier patient group (64.2 (10.2) years; p = 0.0005). After stratification by age, the frequency of mutation carriers was significantly higher for the early onset PD (EOPD, age at onset ⩽50 years) group than for age matched controls (12.9% vs 1.8%; p = 0.0335) and there was a trend towards an increased risk of the mutation carrier with EOPD (odds ratio 8.30; 95% CI 1.45 to 156.53). Clinically, all 16 patients carrying a GBA mutation presented with a typical parkinsonian phenotype and experienced a good or excellent response to levodopa. Conclusions: Mutations of the GBA gene may be associated with the development of EOPD in Taiwan.

Amyloid β (Aβ) plays a major role in the neurodegeneration of Alzheimer's disease (AD). The accumulation of misfolded Aβ causes oxidative stress and inflammatory damage leading to apoptotic cell death. Traditional Chinese herbal medicine (CHM) has been widely used in treating neurodegenerative diseases by reducing oxidative stress and neuroinflammation. We examined the neuroprotective effect of formulated CHM Shaoyao Gancao Tang (SG-Tang, made of Paeonia lactiflora and Glycyrrhiza uralensis at 1:1 ratio) in AD cell and mouse models. In Aβ-GFP SH-SY5Y cells, SG-Tang reduced Aβ aggregation and reactive oxygen species (ROS) production, as well as improved neurite outgrowth. When the Aβ-GFP-expressing cells were stimulated with conditioned medium from interferon (IFN)-γ-activated HMC3 microglia, SG-Tang suppressed expressions of inducible nitric oxide synthase (iNOS), NLR family pyrin domain containing 1 (NLRP1) and 3 (NLRP3), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, attenuated caspase-1 activity and ROS production, and promoted neurite outgrowth. In streptozocin-induced hyperglycemic APP/PS1/Tau triple transgenic (3×Tg-AD) mice, SG-Tang also reduced expressions of NLRP1, NLRP3, Aβ and Tau in hippocampus and cortex, as well as improved working and spatial memories in Y maze and Morris water maze. Collectively, our results demonstrate the potential of SG-Tang in treating AD by moderating neuroinflammation.

Background: Aggregation of misfolded amyloid β (Aβ) in senile plaques causes oxidative stress and neuronal death in Alzheimer's disease (AD). Compounds possessing antiaggregation and antioxidant properties are promising candidate compounds for AD treatment.Methods: We examined the potential of synthetic derivatives of licochalcone A and coumarin for inhibiting Aβ aggregation, scavenging reactive oxygen species (ROS), and providing neuroprotection by using biochemical assays and Tet‐On Aβ‐GFP 293/SH‐SY5Y cell models for AD.Results: Among test compounds, LM‐031, a novel chalcone‐coumarin hybrid, inhibited Aβ aggregation and scavenged free oxygen radicals. LM‐031 markedly reduced Aβ misfolding and ROS as well as promoted neurite outgrowth and inhibited acetylcholinesterase in Tet‐On Aβ‐GFP 293/SH‐SY5Y cells. Mechanistic studies showed upregulation of the HSPB1 chaperone, NRF2/NQO1/GCLC pathway, and CREB/BDNF/BCL2 pathway. Decreased neurite outgrowth upon the induction of Aβ‐GFP was rescued by LM‐031, which was counteracted by knockdown of HSPB1, NRF2, or CREB.Conclusion: Taken together, these findings demonstrate that LM‐031 exhibited antiaggregation, antioxidant, and neuroprotective effects against Aβ toxicity by enhancing HSPB1 and the NRF2‐related antioxidant pathway as well as by activating the CREB‐dependent survival and antiapoptosis pathway. These results imply that LM‐031 may be a new therapeutic compound for AD.

Misfolded tau proteins induce accumulation of free radicals and promote neuroinflammation by activating microglia‐releasing proinflammatory cytokines, leading to neuronal cell death. Traditional Chinese herbal medicines (CHMs) have been widely used in clinical practice to treat neurodegenerative diseases associated with oxidative stress and neuroinflammation. This study examined the neuroprotection effects of formulated CHMs Bai‐Shao (made of Paeonia lactiflora), Gan‐Cao (made of Glycyrrhiza uralensis), and Shaoyao Gancao Tang (SG‐Tang, made of P. lactiflora and G. uralensis at 1 : 1 ratio) in cell model of tauopathy. Our results showed that SG‐Tang displayed a greater antioxidative and antiaggregation effect than Bai‐Shao and Gan‐Cao and a stronger anti‐inflammatory activity than Bai‐Shao but similar to Gan‐Cao. In inducible 293/SH‐SY5Y cells expressing proaggregant human tau repeat domain (ΔK280 tau_RD), SG‐Tang reduced tau misfolding and reactive oxygen species (ROS) level in ΔK280 tau_RD 293 cells and promoted neurite outgrowth in ΔK280 tau_RD SH‐SY5Y cells. Furthermore, SG‐Tang displayed anti‐inflammatory effects by reducing nitric oxide (NO) production in mouse BV‐2 microglia and increased cell viability of ΔK280 tau_RD‐expressing SH‐SY5Y cells inflamed by BV‐2 conditioned medium. To uncover the neuroprotective mechanisms of SG‐Tang, apoptosis protein array analysis of inflamed tau expressing SH‐SY5Y cells was conducted and the suppression of proapoptotic proteins was confirmed. In conclusion, SG‐Tang displays neuroprotection by exerting antioxidative and anti‐inflammatory activities to suppress neuronal apoptosis in human tau cell models. The study results lay the base for future applications of SG‐Tang on tau animal models to validate its effect of reducing tau misfolding and potential disease modification.