APP, PSEN1, and PSEN2 Mutations in Asian Patients with Early-Onset Alzheimer Disease

Giau, Vo Van,Bagyinszky, Eva,Youn, Young Chul,An, Seong Soo A.,Kim, SangYun MDPI AG 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.19

<P>The number of patients with Alzheimer’s disease (AD) is rapidly increasing in Asia. Mutations in the amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes can cause autosomal dominant forms of early-onset AD (EOAD). Although these genes have been extensively studied, variant classification remains a challenge, highlighting the need to colligate mutations across populations. In this study, we performed a genetic screening for mutations in the APP, PSEN1, and PSEN2 genes in 200 clinically diagnosed EOAD patients across four Asian countries, including Thailand, Malaysia, the Philippines, and Korea, between 2009 and 2018. Thirty-two (16%) patients presented pathogenic APP, PSEN1, or PSEN2 variants; eight (25%), 19 (59%), and five (16%) of the 32 patients presented APP, PSEN1, and PSEN2 variants, respectively. Among the 21 novel and known non-synonymous variants, five APP variants were found in Korean patients and one APP variant was identified in a Thai patient with EOAD. Nine, two, and one PSEN1 mutation was found in a Korean patient, Malaysian siblings, and a Thai patient, respectively. Unlike PSEN1 mutations, PSEN2 mutations were rare in patients with EOAD; only three variants were found in Korean patients with EOAD. Comparison of AD-causative point mutations in Asian countries; our findings explained only a small fraction of patients, leaving approximately 84% (p = 0.01) of autosomal dominant pedigrees genetically unexplained. We suggest that the use of high-throughput sequencing technologies for EOAD patients can potentially improve our understanding of the molecular mechanisms of AD.</P>

Gene panels and primers for next generation sequencing studies on neurodegenerative disorders

Vo Van Giau,Seong Soo A. An,Eva Bagyinszky,SangYun Kim 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.2

Several types of neurodegenerative diseases were described, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), prion disease, and Parkinson’s disease (PD). Since the potential treatment strategies of these disorders might be more successful in the pre-clinical stages than in the actual clinical setup, new diagnostic methods were needed. The involvement of heredity in neurodegenerative disorders was established, but several neurodegenerative disorders such as AD, PD, ALS, FTD and Huntington’s disease (HD) are highly complex. Sanger sequencing was used to detect mutations that are causative or risk factors for diseases. The problem with standard sequencing is its high cost and low speed. Recently, next generation sequencing (NGS) strategies were developed, which could provide a more complex genetic analysis of patients with neurodegenerative diseases. In this study, 50 genes were selected, which were established as causative genes for neurodegenerative diseases, but we also included several risk factor genes and candidate genes. Primers (maximum 400-bp length) were designed to screen for mutations and variants in them. We plan to use these primers for NGS screening to create a more detailed genetic profile for these patients. This study could enhance disease diagnosis and would be also helpful in estimating the risk for disease onset in the future.

Recent advances in the treatment of pathogenic infections using antibiotics and nano-drug delivery vehicles

Van Giau, Vo,An, Seong Soo A,Hulme, John Dove Medical Press 2019 Drug design, development and therapy Vol.13 No.-

<P>The worldwide misuse of antibiotics and the subsequent rise of multidrug-resistant pathogenic bacteria have prompted a paradigm shift in the established view of antibiotic and bacterial–human relations. The clinical failures of conventional antibiotic therapies are associated with lengthy detection methods, poor penetration at infection sites, disruption of indigenous microflora and high potential for mutational resistance. One of the most promising strategies to improve the efficacy of antibiotics is to complex them with micro or nano delivery materials. Such materials/vehicles can shield antibiotics from enzyme deactivation, increasing the therapeutic effectiveness of the drug. Alternatively, drug-free nanomaterials that do not kill the pathogen but target virulent factors such as adhesins, toxins, or secretory systems can be used to minimize resistance and infection severity. The main objective of this review is to examine the potential of the aforementioned materials in the detection and treatment of antibiotic-resistant pathogenic organisms.</P>

Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment

Giau, Vo Van,Bagyinszky, Eva,An, Seong Soo A. MDPI AG 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.17

<P>Mild cognitive impairment (MCI) is characterized by a level of cognitive impairment that is lower than normal for a person’s age, but a higher function than that that observed in a demented person. MCI represents a transitional state between normal aging and dementia disorders, especially Alzheimer’s disease (AD). Much effort has been made towards determining the prognosis of a person with MCI who will convert to AD. It is now clear that cerebrospinal fluid (CSF) levels of Aβ40, Aβ42, total tau and phosphorylated tau are useful for predicting the risk of progression from MCI to AD. This review highlights the advantages of the current blood-based biomarkers in MCI, and discusses some of these challenges, with an emphasis on recent studies to provide an overview of the current state of MCI.</P>

Novel PSEN1 p.Gly417Ala mutation in a Korean patient with early-onset Alzheimer's disease with parkinsonism

Giau, Vo Van,Wang, Min Jeong,Bagyinszky, Eva,Youn, Young Chul,An, Seong Soo A.,Kim, SangYun Elsevier Science B.V., Amsterdam. 2018 NEUROBIOLOGY OF AGING Vol.72 No.-

Genetic Factors of Cerebral Small Vessel Disease and Their Potential Clinical Outcome

Giau, Vo Van,Bagyinszky, Eva,Youn, Young Chul,An, Seong Soo A.,Kim, Sang Yun MDPI AG 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.17

<P>Cerebral small vessel diseases (SVD) have been causally correlated with ischemic strokes, leading to cognitive decline and vascular dementia. Neuroimaging and molecular genetic tests could improve diagnostic accuracy in patients with potential SVD. Several types of monogenic, hereditary cerebral SVD have been identified: cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), hereditary diffuse leukoencephalopathy with spheroids (HDLS), COL4A1/2-related disorders, and Fabry disease. These disorders can be distinguished based on their genetics, pathological and imaging findings, clinical manifestation, and diagnosis. Genetic studies of sporadic cerebral SVD have demonstrated a high degree of heritability, particularly among patients with young-onset stroke. Common genetic variants in monogenic disease may contribute to pathological progress in several cerebral SVD subtypes, revealing distinct genetic mechanisms in different subtype of SVD. Hence, genetic molecular analysis should be used as the final gold standard of diagnosis. The purpose of this review was to summarize the recent discoveries made surrounding the genetics of cerebral SVD and their clinical significance, to provide new insights into the pathogenesis of cerebral SVD, and to highlight the possible convergence of disease mechanisms in monogenic and sporadic cerebral SVD.</P>

Application of Linear Programming for cassava starch production optimization in Vietnam within a Circular Economy framework toward Zero emission

Vo Van Giau,Tran Van Thanh,Tran Le Luu,Hans Schnitzer,Le Thanh Hai 대한환경공학회 2023 Environmental Engineering Research Vol.28 No.4

Cassava starch production is a key industrial production of Tay Ninh province, Vietnam. However, this production chain has also caused many negative impacts on the environment. This study applied the principles of circular economy to analyze the waste streams via linear programming method for cassava starch circular production chain towards zero waste emission. The results show that the cassava starch indutry can achieve the goals of zero electricity, zero waste, and zero fossil energy by re-planning the production chain. The chain’s output products are 517.5 tons of bio-oil/year, 206.7 thousand tons of biochar/year, 190.0 thousand tons of dry pulp/year, 10 million m³/year of liquid fertilizer. In order to increase further the value of the chain in the circular economy, future research needs to study the feasibility of a solution to reuse wastewater to produce microalgae, as well as evaluate the effectiveness of these methods. The optimization method applied in this study can also be extended to similar agricultural chains properties such as rice processing, sugar cane, etc.

Clinical genetic strategies for early onset neurodegenerative diseases

Vo Van Giau,Eva Bagyinszky,안성수,SangYun Kim 대한독성 유전단백체 학회 2018 Molecular & cellular toxicology Vol.14 No.2

Purpose of review: Methods for the genetic diagnosis of neurodegenerative disorders were reviewed, including their backgrounds and applications in the laboratory. Majority of disease-causing gene mutations were uncommon in the general population, where dominant variations could be easily identified in certain disorders. The development of molecular, next generation sequencing (NGS) and cytogenetic techniques allowed to identify multiple genetic mutations leading to diseases. Using of the accurate multivariate diagnosis of diseases would be essential for appropriate treatment of patients, genetic counseling and prevention strategies Recent findings: Abnormal genes play an extremely important role in the pathogenesis of neurodegenerative disorders of the nervous system. Many studies of genetic have clearly indicated that the molecular mechanisms underlying the etiology and pathogenesis of most neurodegenerative disorders until now. Mutation is necessary for life, while fidelity is necessary for DNA replication. Mistakes in DNA replication/transcription can cause cells to produce either too much or too little protein or a defective protein. Studies on mutations have revealed the normal functions of genes, messages, proteins, the causes of many diseases, and the variability of responses among individuals. Based on the presence of damaging variants, there are many genes have identified that associated with neurodegenerative disorders through to genetic analyses of patients. This declaration is interesting because also our previous analysis has shown that several types of neurodegenerative diseases associated with abnormal genes function have been well described, including Alzheimer’s disease (AD), front temporal dementia (FTD), amyotrophic lateral sclerosis (ALS), prion disease, and Parkinson’s disease (PD). Since the potential treatment strategies for these disorders may be more successful during the pre-clinical stages than in the actual clinical setup, accurate, simple, and affordable diagnostic methods are needed. A mutation can be defined as a sequence change in a test sample compared to the sequence of a reference standard. This has led to the development of methods for screening and detecting abnormal DNA, including techniques that detect previously described mutations(genotyping) and those that scan for mutations in a particular target region (mutation scanning). This review provides a broad overview of the range of currently available mutation detection techniques with special emphasis on neurodegenerative disorders in humans. We have discussed the methods used for detecting unknown mutations, such as ribonuclease, denaturing gradient-gel electrophoresis, carbodiimide, chemical cleavage, single-strand conformation polymorphism, heteroduplex, and sequencing. Furthermore, other diagnostic methods for testing mutations include allele-specific oligonucleotide hybridization; allele-specific amplification, ligation, primer extension, and the artificial introduction of restriction sites are also reviewed. In order to identify the mutation, the last of the work provides basic insights into some of the most popular in silico tools for splicing defect prediction from the viewpoint of end users.

Optimization of Specific Multiplex DNA Primers to Detect Variable CLU Genomic Lesions in Patients with Alzheimer’s Disease

Vo Van Giau,안성수 한국바이오칩학회 2015 BioChip Journal Vol.9 No.4

Recently, polymorphisms in the clusterin (CLU) or Apolipoprotein J (ApoJ) gene were reported to be involved in lipid metabolism, atherogenesis, and being associated with the risk of developing Alzheimer’s disease (AD). The influences from genetic variation has not been examined among Koreans. To screen genes with abnormal exon expression profiles, we developed PCR primer pairs for CLU gene. The new primer set can target specific regions of previously sequenced CLU gene. Primers were designed to target eight exon amplicons with flanking regions to optimize PCR amplification. One-hundred samples from clinically diagnosed Korean AD patients were selected for testing. We identified four single nucleotide polymorphisms (SNPs) in CLU through direct sequencing of the PCR products. These included three SNPs (rs7982, rs2279590 and rs3216167) that were previously reported variants in the SNP database (dbSNP), which could be found in NCBI. Interestingly, one new (NEW1) or extremely low-frequency mutation was found in more than one individual among the late-onset AD subjects. Our study suggests that CLU variants may also be an AD susceptibility factor among Koreans. Moreover, the findings of the study can be able to develop for simultaneous identify all of the genotypes of CLU mutation sites by DNA microarray PCR-based in the future.

Additional diagnostic testing of the 2019 novel coronavirus (SARS-CoV-2)

Van Giau Vo,Eva Bagyinszky,심규환,Park Yoon Soo,An Seong Soo A. 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.4

Purpose of review Within the last two decades several members of the Coronaviridae family namely Severe Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) have demonstrated epidemic potential. In late, 2019 an unnamed genetic relative, later named SARS-CoV-2 realized its potential in the highly populous neighborhoods of Wuhan, China. Unchecked, the virus rapidly spread among interconnected communities and related households before containment measures could be in acted. “Appropriate” diagnostic testing in response to the SARS-CoV-2 outbreak should be urgently considered. This perspective review gives particular attention to the potential diagnostic testing of the virus in semen and seminal fuids due to its high levels of angiotensin converting enzyme 2 (ACE2) precursor. Recent fndings As many infectious viruses are stable in semen and have transmitted the respective diseases, the presence of SARS-CoV-2 should be tested in semen to assess their stabilities and half-life. As in case of Ebola virus, it was present in semen for longer period in a carrier man without any symptom. Additional hypothesis is that since ACE2 could serve as a mediator for the endocytosis of the previously SARS coronavirus, SARS-CoV-2 may enter the cells through similar mechanism. From the protein expression atlas, high levels of ACE2 precursor were found in intestines and testis. Hence, the testis and seminal fuids could be the host cell and/or reservoir. The results could be used as a suggestive guideline for the sexual activities after the discharge or declaration of disease free.