Analysis of 12 GWAS-Linked Loci With Parkinson's Disease in the Chinese Han Population.

A recent large-scale European-originated genome-wide association study identified 38 novel independent risk signals in 37 loci for Parkinson's disease (PD). However, whether these new loci are associated with PD in Asian populations remains elusive. The present study aimed to explore the relationship between the 12 most relevant loci with larger absolute values for these new risk loci and PD in the Chinese Han population. We performed a case-control study including 527 PD patients and 435 healthy controls. In the allele model, it was found that rs10748818/GBF1 was associated with PD in the Chinese Han population [p = 0.035, odds ratio (OR) 1.221, 95% confidence interval (CI) 1.014-1.472.

α-Synuclein in Parkinson's Disease: Does a Prion-Like Mechanism of Propagation from Periphery to the Brain Play a Role?

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, defined as motor and non-motor symptoms associated with the loss of dopaminergic neurons and a decreased release of dopamine (DA). Currently, PD patients are believed to have a neuropathological basis denoted by the presence of Lewy bodies (LBs) or Lewy neurites (LNs), which mostly comprise α-synuclein (α-syn) inclusions. Remarkably, there is a growing body of evidence indicating that the inclusions undergo template-directed aggregation and propagation via template-directed among the brain and peripheral organs, mainly in a prion-like manner. Interestingly, some studies reported that an integral loop was reminiscent of the mechanism of Parkinson's disease, denoting that α-syn as prionoid was transmitted from the periphery to the brain via specific pathways. Also the systematic life cycle of α-syn in the cellular level is illustrated. In this review, we critically assess landmark evidence in the field of Parkinson's disease with a focus on the genesis and prion-like propagation of the α-syn pathology. The anatomical and cell-to-cell evidences are discussed to depict the theory behind the propagation and transferred pathways. Furthermore, we highlight effective therapeutic perspectives and clinical trials targeting prion-like mechanisms. Major controversies surrounding this topic are also discussed.

Composite Polymer Electrolyte Incorporating Metal-Organic Framework Nanosheets with Improved Electrochemical Stability for All-Solid-State Li Metal Batteries.

Composite polymer electrolytes using polyethylene oxide (PEO) are highly appealing by virtue of the fine electrochemical stability, inexpensiveness, and easy fabrication. However, their practical application is currently hindered by the insufficient room-temperature ionic conductivity. Herein, nickel-based ultrathin metal-organic framework nanosheets (NMS) are first introduced as a novel 2D filler into the PEO matrix. The introduction of NMS with a high aspect ratio effectively improves the amorphous region proportion of PEO and thus enhances the ionic conductivity of the electrolyte by 1 order of magnitude. In addition, the Lewis acid-base interactions between the surface-coordinated unsaturated Ni atoms in NMS and the anions of lithium salt could promote the dissociation of lithium salt. Hence, the composite electrolyte with NMS achieves a high Li+ transference value of 0.378. Along with the unique nanostructure of NMS, this NMS composite electrolyte also suppresses Li dendrite growth during cycling. As a result, the assembled all-solid-state Li/LiFePO4 battery demonstrates a high reversible capacity of 130 mA h g-1 at 0.1 C and 30 °C for 50 cycles.

Modeling Parkinson's Disease Using Induced Pluripotent Stem Cells.

Parkinson's disease (PD) is the second most common neurodegenerative disease. The molecular mechanisms of PD at the cellular level involve oxidative stress, mitochondrial dysfunction, autophagy, axonal transport, and neuroinflammation. Induced pluripotent stem cells (iPSCs) with patient-specific genetic background are capable of directed differentiation into dopaminergic neurons. Cell models based on iPSCs are powerful tools for studying the molecular mechanisms of PD. The iPSCs used for PD studies were mainly from patients carrying mutations in synuclein alpha (SNCA), leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PARK2), cytoplasmic protein sorting 35 (VPS35), and variants in glucosidase beta acid (GBA). In this review, we summarized the advances in molecular mechanisms of Parkinson's disease using iPSC models.

Association analysis of 15 GWAS-linked loci with Parkinson's disease in Chinese Han population.

Genetic factors play an important role in Parkinson's disease (PD) and vary from different races. A previous genome-wide association study (GWAS) identified 17 novel risk loci that were associated with PD in Caucasians. Several subsequent studies investigated the association between these loci and PD in Chinese populations. However, the results on the role of these variants for PD have been conflicting. To explore the relationship of 15 controversial loci with PD in the Chinese Han population, we performed a case-control study including 492 PD patients and 524 healthy controls. iMLDR technology was used to type 15 GWAS-linked loci of 1016 blood samples from all subjects. We found that rs34043159 (IL1R2) (dominant model after adjusted: p = 0.011, OR 95 % CI 0.577 (0.378-0.880)) and rs4073221 (SATB1) (allele model: p = 0.001, OR 95 % CI 0.542 (0.371-0.792); dominant model after adjusted: p = 0.049, OR 95 % CI 0.587 (0.345-0.998)) were associated with PD. After age onset and gender subgroup analysis, rs34043159 (IL1R2) (χ2 = 7.971, p = 0.019) and rs4073221 (SATB1) (χ2 = 12.673, p = 0.001) were associated with late-onset PD. rs34043159 (IL1R2) was associated with PD in females (χ2 = 7.227, p = 0.027) rather than males (χ2 = 1.100, p = 0.577). rs4073221 (SATB1) was associated with PD in both males (χ2 = 10.270, p = 0.005) and females (χ2 = 7.050, p = 0.022). Further studies are needed to explore the role of IL1R2 and SATB1 in the pathogenesis of PD.

Tape-Casting Li0.34 La0.56 TiO3 Ceramic Electrolyte Films Permit High Energy Density of Lithium-Metal Batteries.

Ceramic oxide electrolytes are outstanding due to their excellent thermostability, wide electrochemical stable windows, superior Li-ion conductivity, and high elastic modulus compared to other electrolytes. To achieve high energy density, all-solid-state batteries require thin solid-state electrolytes that are dozens of micrometers thick due to the high density of ceramic electrolytes. Perovskite-type Li0.34 La0.56 TiO3 (LLTO) freestanding ceramic electrolyte film with a thickness of 25 µm is prepared by tape-casting. Compared to a thick electrolyte (>200 µm) obtained by cold-pressing, the total Li ionic conductivity of this LLTO film improves from 9.6 × 10-6 to 2.0 × 10-5 S cm-1 . In addition, the LLTO film with a thickness of 25 µm exhibits a flexural strength of 264 MPa. An all-solid-state Li-metal battery assembled with a 41 µm thick LLTO exhibits an initial discharge capacity of 145 mAh g-1 and a high capacity retention ratio of 86.2% after 50 cycles. Reducing the thickness of oxide ceramic electrolytes is crucial to reduce the resistance of electrolytes and improve the energy density of Li-metal batteries.

SNCA but not DNM3 and GAK modifies age at onset of LRRK2-related Parkinson's disease in Chinese population.

BACKGROUND: Recently, rs2421947 in DNM3 (dynamin 3) was reported as a genetic modifier of age at onset (AAO) of LRRK2 G2019S-related Parkinson's disease (PD) in a genome-wide association study in Arab-Berber population. Rs356219 in SNCA (α-synuclein) was also reported to regulate the AAO of LRRK2-related PD in European populations, and GAK (Cyclin G-associated kinase) rs1524282 was reported to be associated with an increased PD risk with an interaction with SNCA rs356219. G2019S variant is rare in Asian populations, whereas two other Asian-specific LRRK2 variants, G2385R and R1628P, are more frequent with a twofold increased risk of PD. METHODS: In this study, we investigated whether rs2421947, rs356219 and rs1524282 modified AAO in LRRK2-related PD patients in Han Chinese population. We screened LRRK2 G2385R and R1628P variants in 732 PD patients and 1992 healthy controls, and genotyped DNM3 rs2421947, SNCA rs356219 and GAK rs1524282 among the LRRK2 carriers. RESULTS: The SNCA rs356219-G allele was found to increase the risk of PD in LRRK2 carriers (OR 1.50, 95%CI 1.08-2.01, P = 0.016), and the AAO of AG + GG genotypes was 4 years earlier than AA genotype (P = 0.006). Nonetheless, no similar association was found in DNM3 rs2421947 and GAK rs1524282. CONCLUSIONS: Our results show that SNCA but not DNM3 or GAK is associated with AAO of LRRK2-PD patients in Chinese population.

New Insights Into the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD), a common neurodegenerative disease in the elderly and the most prevalent cause of dementia, is characterized by progressive cognitive impairment. The prevalence of AD continues to increase worldwide, becoming a great healthcare challenge of the twenty-first century. In the more than 110 years since AD was discovered, many related pathogenic mechanisms have been proposed, and the most recognized hypotheses are the amyloid and tau hypotheses. However, almost all clinical trials targeting these mechanisms have not identified any effective methods to treat AD. Scientists are gradually moving away from the simple assumption, as proposed in the original amyloid hypothesis, to new theories of pathogenesis, including gamma oscillations, prion transmission, cerebral vasoconstriction, growth hormone secretagogue receptor 1α (GHSR1α)-mediated mechanism, and infection. To place these findings in context, we first reviewed the neuropathology of AD and further discussed new insights in the pathogenesis of AD.

DNAJC12 mutation is rare in Chinese Han population with Parkinson's disease.

Recently, mutations of DNAJC12 gene were reported to be associated with early-onset parkinsonism, progressive neurodevelopmental delay, and dystonia in several unrelated pedigrees. This study aimed to evaluate DNAJC12 coding mutations in sporadic Chinese Han patients with Parkinson's disease (PD) and test whether an age-of-onset effect exists. Seven hundred two Chinese Han sporadic PD patients, including 181 early-onset PD and 521 late-onset PD, and 728 healthy controls were recruited. No documented disease-causing mutation of DNAJC12 was identified, but we found 7 single-nucleotide polymorphisms. Allele frequencies did not differ between all the PD patients and controls or between any 2 subgroups for all these single-nucleotide polymorphisms. Our study suggests that DNAJC12 mutation is not a risk factor of PD in Chinese Han population, and no age-of-onset effect was verified.