차세대 신약개발의 주역, 바이오벤처를 찾아서 ; Zinc finger를 이용한 유전자의 전사조절 기술을 산업화는 회사, (주)툴젠

설원기,김진수 생화학분자생물학회 2002 생화학분자생물학회 소식 Vol.22 No.4

가족성 파킨슨병의 원인 유전자

설원기 대한정신약물학회 2008 대한정신약물학회지 Vol.19 No.1

Extended treatment using specific medicines for Parkinson’s disease (PD) or psychotic disorders often induces symptoms related to psychotic disorders or PD, respectively. PD is the second most common neurodegenerative disease. Most cases of PD occur sporadically, but approximately 5–10% of cases are inherited as familial PD (FPD). Identification of the genes responsible for FPD, as well as their function, is essential to clarify the pathogenic mechanism of PD. Recent genomic analyses using samples obtained from patients with FPD have mapped 13 PARK loci and have identified SNCA, LRRK2, parkin, PINK1, DJ-1, ATP13A2 and UCHL1 as genes causing PD in those loci. This review discusses the results of recent studies on these PD genes. 파킨슨병이나 정신병성 장애 환자에서 특정 치료 약물의 장기적인 복용은 종종 각각 정신병성 장애나 파킨슨병 증세를 유발한다. 파킨슨병은 두번째로 많이 발병하는 퇴행성신경질환이다. 대부분의 파킨슨병은 산발적으로 생기지만 약 5-10%의 환자는 가족성으로 유전되어 나타난다. 파킨슨병의 병리학적 기작을 이해하려면 이들 가족성 파킨슨병 (familial Parkinson’s disease: FPD)의 원인이 되는 유전자를 찾아내고, 그 기능을 밝히는 연구가 필수적이다. 가족성 파킨슨병 환자 시료를 사용한 최근의 유전체적 분석은 13개의 PARK 유전자자리를 염색체상에 지도화하였고, SNCA, LRRK2, parkin, PINK1, DJ-1, ATP13A2, UCHL1을 각 PARK 위치에 있는 파킨슨병 원인 유전자로 동정하였다. 이 종설은 이들 파킨슨병 유전자의 최근 연구 결과에 대해 고찰하였다.

커피, 담배, 술이 파킨슨병에 미치는 영향

설원기,김혜정,손일홍 대한신경과학회 2021 대한신경과학회지 Vol.39 No.3

Since the neuroprotective effects of coffee and tobacco on Parkinson’s disease have been reported more than 50 years ago, clinical studies using caffeine and nicotine that were presumed as effective components of coffee and tobacco, respectively, are being actively executed. However, most results failed to show significant differences between the tested and control groups, and some studies revealed contradictory results to the neuroprotection. The reason for this might be that the effective components are something other than nicotine or caffeine, and/or differences to design the clinical trials such as patients recruiting, prescribed amount and period, and analyzed criteria etc. The review summarizes recent results for effect of coffee, tobacco as well as alcohol, representatives of indulgent food, on Parkinson’s disease.

Urinary Biomarkers for Neurodegenerative Diseases

설원기,김혜정,Il Hong Son 한국뇌신경과학회 2020 Experimental Neurobiology Vol.29 No.5

Global incidence of neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) is rapidly increasing, but the diagnosis of these diseases at their early stage is challenging. Therefore, the availability of reproducible and reliable biomarkers to diagnose such diseases is more critical than ever. In addition, biomarkers could be used not only to diagnose diseases but also to monitor the development of disease therapeutics. Urine is an excellent biofluid that can be utilized as a source of biomarker to diagnose not only several renal diseases but also other diseases because of its abundance in invasive sampling. However, urine was conventionally regarded as inappropriate as a source of biomarker for neurodegenerative diseases because it is anatomically distant from the central nervous system (CNS), a major pathologic site of NDD, in comparison to other biofluids such as cerebrospinal fluid (CSF) and plasma. However, recent studies have suggested that urine could be utilized as a source of NDD biomarker if an appropriate marker is predetermined by metabolomic and proteomic approaches in urine and other samples. In this review, we summarize such studies related to NDD.

Rab GTPases as Physiological Substrates of LRRK2 Kinase

설원기,남다름,손일홍 한국뇌신경과학회 2019 Experimental Neurobiology Vol.28 No.2

LRRK2 (Leucine-Rich Repeat Kinase 2) is a gene whose specific mutations cause Parkinson’s disease (PD), the most common neurodegenerative movement disorder. LRRK2 harbors GTPase and kinase activities, two enzyme activities that play critical roles in the regulation of cellular signal transduction. Among the several LRRK2 pathogenic mutations, the most prevalent G2019S mutation increases its kinase activity when compared with the wild-type (WT), suggesting that LRRK2 kinase substrates are potential culprits of PD pathogenesis. Although there were several studies to identify LRRK2 kinase substrates, most of them mainly employed in vitro kinase assays. Therefore, it remains uncertain whether the identified substrates were real physiological substrates. However, efforts to determine physiological LRRK2 kinase substrates have recently identified several members of the Rab GTPase family as physiological LRRK2 kinase substrates. A conserved threonine or serine in the switch II domain of certain Rab GTPase family members (Rab3A/B/C/D, Rab5A/B, Rab8A/B, Rab10, Rab12, Rab29, Rab35 and Rab43) has been pinpointed to be phosphorylated by LRRK2 in cells using sophisticated phosphoproteomics technology in combination with LRRK2-specific kinase inhibitors. The Rab GTPases regulate vesicle trafficking, suggesting that LRRK2 may be a regulator of such vesicle trafficking, confirming previously suggested LRRK2 functions. However, how the consequence of the LRRK2-mediated Rab phosphorylation is related to PD pathogenesis is not clear. This review briefly summarizes the recent results about LRRK2-mediated Rab phosphorylation studies.

국가지정연구실(NRL)소개 : 게놈 조절연구실 -Zine finger를 이용한 유전자의 전사조절과 그 응용-

설원기,박경순,김진수 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 2002 생물산업 Vol.15 No.4

가족성 파킨슨병의 원인 유전자

대한정신약물학회 2008 대한정신약물학회지 Vol.19 No.2

Rhodopseudomonas sp . KCTC 1437 의 수소생성에 있어서의 Hydrogenase 와 Nitrogenase 의 관계

설원기(Won Gi Seol),고영희(Yung Hee Kho) 한국미생물생명공학회 1986 한국미생물·생명공학회지 Vol.14 No.5

Effect of leucine-rich repeat kinase 2 (LRRK2) on protein synthesis

김혜정,손일홍,설원기 한국통합생물학회 2018 Animal cells and systems Vol.22 No.1

Mutations in the leucine-rich repeat kinase 2 (LRRK2) cause Parkinson’s disease (PD) in an autosomal dominant manner. Pathogenic mutations of LRRK2 such as G2019S and R1441C have been observed as common genetic causes of PD. Recently, LRRK2 has been reported to increase the reporter protein synthesis in both cap-dependent and -independent manners via phosphorylation of the ribosomal protein RPS15. In this study, we tested whether LRRK2 recombinant protein would directly increase protein synthesis using a well-defined in vitro coupled transcription/translation system. Addition of commercial full-length LRRK2 or GST-fused N-terminal-deleted LRRK2 recombinant proteins to the system showed no change of protein synthesis, as measured by luciferase reporter activity. In addition, the SUnSET assay to measure newly synthesized cellular proteins showed that G2019S overexpression had a minimal effect on the total protein amount. However, we confirmed the previous result that G2019S overexpression increased the amount of protein synthesized from an exogenous gene, Flag- VAMP2, which was transfected as a reporter, whereas there was no significant change in the amount of the Flag-VAMP2 mRNA. Inhibition of protein degradation showed that protein accumulation in the vector control was higher than that of the G2019S overexpression vector. Our results suggest that LRRK2 protein influences the amount of protein by inhibiting protein degradation rather than by directly stimulating translation.

Unstable Repeat Expansion in Neurodegenerative Dementias: Mechanisms of Disease

양현덕,호동환,설원기 대한치매학회 2012 Dementia and Neurocognitive Disorders Vol.11 No.1

The majority of neurodegenerative dementias are thought to result primarily from the misfolding, aggregation and accumulation of proteins which interfere with protein homeostasis in the brain. Some of them are caused by the expansion of unstable nucleotide repeats, which include Huntington’s disease as a prototype. Other neurodevelopmental or neurodegenerative disorders, such as fragile X syndrome, some spinocerebellar ataxias and myotonic dystrophies exhibit cognitive or behavioral deficits as parts of their clinical manifestations. Unstable repeat expansions include trinucleotide, tetranucleotide, and pentanucleotide. Recently hexanucleotide repeat expansion in frontotemporal dementia and amyotrophic lateral sclerosis was identified. The pathogenic mechanisms for these repeat disorders include either loss of protein function or gain of function at the protein or RNA levels. The aim of this article is to review proposed mechanisms by which unstable repeat expansions give rise to degeneration of brain with the hope of understanding the diseases and providing insights into the areas of therapeutic intervention. We will review these potential mechanisms in the context of fragile X syndrome, Huntington’s disease, spinocerebellar ataxias, myotonic dystrophy, and frontotemporal dementia and amyotrophic lateral sclerosis. We will also discuss the potential targets for therapeutic intervention.