Ubiquitin proteasome system networks in the neurological disorders

Mrudhula Anuppalle,이명철,Sateesh Maddirevula,허태린 한국통합생물학회 2013 Animal cells and systems Vol.17 No.6

Human neurological disorders are associated with brain-enriched proteins in a major way. Homeostasis of such proteins is a critical event in brain functioning and development. Neuropathological studies of most common neurological disorders clearly show that accumulated, misfolded, mutant proteins are the preliminary causes for such disorders. Studies in the past few decades suggest that the ubiquitin proteasome system (UPS) network is a critical regulator of protein levels mammalian cells. To date, various proteins and substrates in UPS associated with neurological disorders have been identified, but molecular mechanisms and how they are associated with pathogenesis of neurological disorders are poorly understood. Understanding UPS network may set a new window to understand the pathogenesis of neurological disorders. Here we are reporting the current studies of UPS components in major neurological disorders, such as Parkinson’s, Alzheimer’s, autistic spectrum disorders, Huntington’s, and multiple sclerosis.

신생아 중환자실에서의 신경학적 질환의 빈도와 관련인자

김동원(Dong Won Kim),서은숙(Eun Sook Suh) 대한소아신경학회 2002 대한소아신경학회지 Vol.10 No.2

목 적:사회경제적 발달과 신생아 집중 치료실의 질향상 및 의료발달, 미숙아 출생예방 등으로 신생아 중환자의 생존율이 증가하고 있다. 이로 인해 신경학적 질환의 빈도는 증가하고 있다. 이에 저자들은 신생아 중환자실에서의 신경학적 질환의 종류와 빈도, 재태 연령과 체중과의 연관성, 사망률과 생존자들에서의 신경학적 장애 경향을 알아보고자 한다. 방 법:1997년 1월부터 2001년 12월까지 순천향대학교병원 신생아 중환자실에 입원한 1,399명의 신생아 중 두개내 출혈, 신생아 경련, 저산소 허혈성 뇌증, 중추 신경계 감염증, 중추 신경계 기형 및 염색체 이상 중 1개 이상의 신경 질환을 진단 받았던 156명을 후향적 방법으로 조사, 분석하였다. 결 과:연구 기간동안 신경학적 이상이 있었던 156명의 신생아들은 총 193개의 신경학적 이상이 있었다. 신생아 사망률은 1997년에 0.9%, 2001년에 0.8%로 1997년에 비해 2001년에는 11.1% 감소하였다. 신경 질환의 빈도는 1997년에 3.2%, 2001년에 11.5%로 1997년에 비해 약 3.6배 증가하였다. 신생아 중환자실의 신경학적 이상이 없었던 환아의 사망률은 1997년에 4.7%, 2001년에 2.4%로 5년간 감소하였으나, 신경학적 이상이 있었던 환아의 사망률도 1997년에 5.6%, 2001년에 5.5%로 비슷하였다. 156명 중 두개내 출혈이 134명(1997년에 5.0%, 2001년에 38.2%), 신생아 경련이 28명(1997년에 0.6%, 2001년에 6.0%), 저산소성 허혈성 뇌손상이 24명(1997년에 2.2%, 2001년에 2.3%),중추신경계 감염증이 2명, 중추신경계 기형 및 염색체 이상이 5명(1997년에 0.3%, 2001년에 0.9%)이었다. 5년간의 연구기간동안 신생아 경련과 두개내 출혈 빈도는 증가하는 추세이며 저산소성 허혈성뇌증은 큰 변화가 없었다. 결 론:1997년에서 2001년 동안 신생아 중환자실의 생존률은 향상되었으나, 신경 질환의 이환률은 증가하였다. 신생아의 신경 질환의 예방을 위해 미숙아 분만의 예방과 두부 초음파의 선별검사 등의 노력이 필요할 것으로 사료되며, 이들 환자의 장기적인 예후에 대한 보다 많은 연구가 필요할 것으로 사료된다. Purpose: Recent neonatal care unit survival rates have improved. These increasing survival rates have resulted in increased neurologic disorders. So we investigated the sorts and frequency of neurologic disorders at neonatal intensive care unit, association between gestational age and birthweight, neonatal mortality and tendency of neurologic disorders in survivors. Methods: Retrospective reviews were made on 156 cases with one or more neurologic disorder of 1,399 neonates, who were admitted to the neonatal intensive care unit, Soonchunhyang Hospital from January 1997 to December 2001. Neurologic disorders were categorized into five groups:intraventricular hemorrhage, neonatal seizures, hypoxic- ischemic encephalopathy, central nervous system infection and central nervous system congenital malformations and chromosomal aberrations. Results: Over the study period, 156 cases with neurologic disorders had a total of 193 neurologic disorders. The frequency of neurologic disorders increased from 3.2% in 1997 to 11.5% in 2001, while the neonatal mortality rates in intensive care unit have declined from 4.8% in 1997 to 3.7% in 2001. In 156 neonates, 134 had intraventricular hemorrhage, 28 had seizures, 24 had hypoxic-ischemic encephalopathy, 2 had central nervous system infections and 5 had congenital central nervous system malformation and chromosomal aberration. Frequencies of intraventricular hemorrhage and seizure has increased, but, that of hypoxic-ischemic encephalopathy has not changed, for the 5 years. Conclusion: Neonatal intensive care unit survival rates have improved for 5 years, but, the neurologic morbidity rates have increased. Because neurologic disorders have great influence on the long-term neurologic disability, early detection and treatment of neurologic disorders is important.

대한민국 군인의 신경계 질환의 역학적 동향에 대한 연구

박성진 ( Sungjin Park ) 국군의무사령부 2018 대한군진의학학술지 Vol.49 No.1

Objectives; This study was performed to evaluate the current status of neurological disorders in soldiers of Republic of Korea. Methods; The neurological disorders treated in outpatient clinics of 14 Republic of Korea Armed Forces hospitals in the period from 2013 to 2017 were retrospectively analyzed. Results; The total number of visiting outpatient clinic due to neurological disorders was 69,547. Headache was the most common disorder(44.1%). The number of patients treated with migraine and abnormal involuntary movement were annually increased(Ptrend = 0.014, both), and in addition, the proportion of the two disorders were also annually increased from 2.5% in 2013 to 7.1% in 2017 for migraine and 0.6% in 2013 to 1.5% in 2017 for abnormal involuntary movement(Ptrend of percent change = 0.014 and 0.023, respectively). Dizziness(8.1%), syncope and collapse(4.5%), and mono-neuropathy(2.9%) were also common disorders. The distribution of neurological disorders was not significantly different between militaryㆍair-force hospitals and naval hospitals, as well as between naval hospitals. Conclusion; This is the first report presenting the current status of neurological disorders in soldiers of Republic of Korea. Further policies are needed to be considered for the better management of the neurological disorders.

Reveiw Article : Mesenchymal Stem Cells for Treatment of Neurological Disorders: a Paracrine Effect

( Moon Hang Kim ),( Kil Hwan Kim ),( So Ra Park ),( Byung Hyune Choi ) 한국조직공학과 재생의학회 2013 조직공학과 재생의학 Vol.10 No.5

Mesenchymal stem cells (MSCs) have been emerged as a potential therapeutic modality for stem cellbased therapy and tissue engineering based on their self-renewal ability and multipotency. However, recent knowledge about MSCs biology and therapeutic concept suggests that MSCs can offer therapeutic benefits by secretion of soluble factors rather than by differentiating into target cells and reconstituting damaged tissues by themselves. Many studies show that MSCs produce a wide variety of growth factors, cytokines, chemokines, angiogenic factors, and extracellular matrix (ECM) molecules that act on themselves or neighboring cells eventually to promote regeneration of injured tissues, stimulate differentiation or proliferation of endogenous cells, and modulate host immune responses and inflammation. In the cases of neurological disorders, implanted MSCs have shown low differentiation ability into three neural cell types and limited long-time survival. Recent studies rather suggest that the therapeutic effect of MSCs on neurological disorders can also be attributed to their paracrine effects. In this review, we will introduce these recent studies on the paracrine effects and therapeutic utility of MSCs on diverse neurological disorders including neurodegenerative diseases, stroke and traumatic injuries in the brain and spinal cord.

Evaluation of relationships between psoriasis and neurologic disorder using sequential pattern mining

( Ju Hee Han ),( Jong Soo Jeon ),( Jae Woong Yoon ),( Jae Yeon Ryu ),( Chul Hwan Bang ),( Jun Young Lee ),( Young Min Park ),( Suk Jun Lee ),( Ji Hyun Lee ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

Background: Psoriasis can be also associated with a various systemic comorbidities. Although it is still under debate, psoriasis is considered to be associated with some neurologic conditions such as migraine, headache, sleep disorder and neuropathies. Objectives: To identify the relationship between psoriasis and neurologic disorders in the reality through a population-based study using Sequential pattern mining (SPM). Methods: We obtained population-based data recorded from 2011 to 2013 by the Health Insurance Research and Assessment Agency. The cases of psoriasis and neurologic disorders were identified using the diagnostic codes of the International Classification of Diseases 10th Revision. SPM was used to identify the comorbidities and measure the time onset of the comorbidities. Results: Patients with psoriasis had a higher comorbidity of headache and migraine (comorbidity: 0.235% and 0.18%, respectively) than other neurologic disorders. Sleep disorder (comorbidity: 0.125%), mononeuropathies (comorbidity: 0.12%), transient cerebral ischemic attack (comorbidities: 0.047%) and polyneuropathies (comorbidities: 0.0008%) were also related with psoriasis. Headache, migraine, sleep disorder and mononeuropathies was diagnosed 229.3, 178.3, 148.1 and 214.7 days after the diagnosis of psoriasis, respectively. Conclusion: These results suggest that it is necessary to keep in mind a possibility of neurological disorder for proper management.

미국 형사법 실무에서의 뇌과학 증거 활용에 관한 고찰

이인영 ( Lee In Young ) 홍익대학교 법학연구소 2017 홍익법학 Vol.18 No.1

미국의 형사법 실무에서는 뇌과학은 상당한 영향력을 행사하고 있다. 수백건의 형사사건이 뇌생물학적 주장에 영향을 받았으며 빈번하게 뇌과학 증거가 제출되고 법정에서 인용되고 있는 실정이다. 본 연구에서는 뇌영상기술의 발달과 뇌과학증거의 다양한 유형들을 살펴보고, 법정 증거로서의 수용가능성, 증거능력 및 위험요소들을 검토하였다. (II) `맥아더 법과 뇌과학 프로젝트`에서 이루어진 Nita Farahany 교수의 조사연구결과를 소개하여 캘리포니아 주 공판 법정에서 얼마나 자주 뇌영상의 증거가 소개되는지와 법정에서의 뇌영상 증거에 대한 유형, 방어내용, 인용율 등을 살펴보았다.(III) 실제로 피고인들이 법정에서 뇌과학 증거 활용을 하는 분야들에 대해서 살펴보고 기능적 의미와 성공적 결과를 가져오는지 여부에 대해서도 설명하였다.(IV) 마지막으로 향후 우리나라에서도 뇌과학 증거가 수용되고 양형감경요소 내지 유무죄 사실인정의 근거, 또는 재범예측인자로 활용되기 위해서 어떠한 준비과정 내지 대응방안이 있어야 할 것인가에 대한 시사점을 얻을 수 있도록 고찰 하였다.(V) Neuroscience research holds promise for improving our understanding of human behavior, motivation, intention, and action. Advances in neuroscience over recent decades led to development of treatments for certain debilitating neurological disorders. Neuroscience has become an integral part of the criminal justice system in the United States. During the past decade, hundreds of criminal cases have been influenced by neurobiological claims. The use of neurological evidence in the criminal courtroom is on the rise. According to a recent study, over 1500 judicial opinions issued during 2005- 2012 discuss the use of neuroscience by criminal defendants. Many of these cases include expert evidence about past head or brain trauma, neuropsychological testing, and neuroimaging studies conducted. Neuroscience evidence has been introduced and employed at various stages. Defendants have argued that they should be held less accountable for their actions or punished less severely because of alleged neurological impairments. Prosecutors have seized upon the double-edged potential of such evidence to indict defendants` characters or underscore future dangerousness. Many courts in United States have admitted neuroimaging evidence, and more will follow as the science underlying neuroimaging becomes more generally accepted. Maybe neuroscience evidence will be accepted before long in Korea. When a judge has to decide whether to admit neuroscience evidence, the rules of evidence provide clear guidelines regarding when and for what purpose such evidence can be introduced in Korea.

Curcumin, Inflammation, and Neurological disorders: How are they linked?

Garodia Prachi,Hegde Mangala,Kunnumakkara Ajaikumar B.,Aggarwal Bharat B. 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.3

Background : Despite the extensive research in recent years, the current treatment modalities for neurological disorders are suboptimal. Curcumin, a polyphenol majorly found in Curcuma genus, has been shown to mitigate the pathophysiology and clinical sequalae involved in neuroinflammation and neurodegenerative diseases. Methods : We searched PubMed database for relevant publications on curcumin and its uses in treating neurological diseases. We also reviewed relevant clinical trials which appeared on searching PubMed database using ‘Curcumin and clinical trials’. Results : This review details the pleiotropic immunomodulatory functions and neuroprotective properties of curcumin, its derivatives and formulations in various preclinical and clinical investigations. The effects of curcumin on neurodegenerative diseases such as Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), brain tumors, epilepsy, Huntington's disorder (HD), ischemia, Parkinson's disease (PD), multiple sclerosis, and traumatic brain injury (TBI) with a major focus on associated signalling pathways have been thoroughly discussed. Conclusion : This review demonstrates curcumin can suppress spinal neuroinflammation by modulating diverse astroglia mediated cascades, ensuring the treatment of devastating neurological disorders.

Functional polarization of neuroglia: Implications in neuroinflammation and neurological disorders

Jha, M.K.,Lee, W.H.,Suk, K. Pergamon Press 2016 Biochemical pharmacology Vol.103 No.-

<P>Recent neuroscience research has established the adult brain as a dynamic organ having a unique ability to undergo changes with time. Neuroglia, especially microglia and astrocytes, provide dynamicity to the brain. Activation of these glial cells is a major component of the neuroinflammatory responses underlying brain injury and neurodegeneration. Glial cells execute functional reaction programs in response to diverse microenvironmental signals manifested by neuropathological conditions. Activated microglia exist along a continuum of two functional states of polarization namely M1-type (classical/proinflammatory activation) and M2-type (alternative/anti-inflammatory activation) as in macrophages. The balance between classically and alternatively activated microglial phenotypes influences disease progression in the CNS. The classically activated state of microglia drives the neuroinflammatory response and mediates the detrimental effects on neurons, whereas in their alternative activation state, which is apparently a beneficial activation state, the microglia play a crucial role in tissue maintenance and repair. Likewise, in response to immune or inflammatory microenvironments astrocytes also adopt neurotoxic or neuroprotective phenotypes. Reactive astrocytes exhibit two distinctive functional phenotypes defined by pro- or anti-inflammatory gene expression profile. In this review, we have thoroughly covered recent advances in the understanding of the functional polarization of brain and peripheral glia and its implications in neuroinflammation and neurological disorders. The identifiable phenotypes adopted by neuroglia in response to specific insult or injury can be exploited as promising diagnostic markers of neuroinflammatory diseases. Furthermore, harnessing the beneficial effects of the polarized glia could undoubtedly pave the way for the formulation of novel glia-based therapeutic strategies for diverse neurological disorders. (C) 2015 Elsevier Inc. All rights reserved.</P>

Induced pluripotent stem cells for modeling of pediatric neurological disorders.

Jang, Jiho,Quan, Zhejiu,Yum, Yunjin J,Song, Hyo Sook,Paek, Seonyeol,Kang, Hoon-Chul Wiley 2014 Biotechnology Journal Vol.9 No.7

<P>The pathophysiological mechanisms underlying childhood neurological disorders have remained obscure due to a lack of suitable disease models reflecting human pathogenesis. Using induced pluripotent stem cell (iPSC) technology, various neurological disorders can now be extensively modeled. Specifically, iPSC technology has aided the study and treatment of early-onset pediatric neurodegenerative diseases such as Rett syndrome, Down syndrome, Angelman syndrome. Prader-Willi syndrome, Friedreich's ataxia, spinal muscular atrophy (SMA), fragile X syndrome, X-linked adrenoleukodystrophy (ALD), and SCN1A gene-related epilepsies. In this paper, we provide an overview of various gene delivery systems for generating iPSCs, the current state of modeling early-onset neurological disorders and the ultimate application of these in vitro models in cell therapy through the correction of disease-specific mutations.</P>

Role of Core-Based Exercises in Improving Proprioception among Individuals with Neurological Disorders: A Systematic Literature Review and Meta-Analysis

Hyeong-Chan Lee,Jae-Hoon Lee,Min-Seong Ha 한국운동생리학회 2024 운동과학 Vol.33 No.2

PURPOSE: This study aimed to validate the effect of core-based exercise on proprioception in individuals with neurological disorders through a systematic review and meta-analysis. METHODS: A systematic literature search was conducted using databases such as PubMed, Web of Science, and Scopus for studies published up to October 10, 2023. The search yielded 1,945 articles, with seven studies ultimately included for in-depth analysis. Meta-analanalysis was performed using Review Manager 5.4 software. Standardized mean differences (SMDs) were calculated using Hedges’ g value using both random-effects and fixed-effects models. RESULTS: The meta-analysis revealed that core-based exercise significantly improved joint position sense (SMD=-1.33; 95% confidence interval [CI]=-2.09 to -0.57; I²=0%; p<.001) and kinesthesia (SMD=-0.33; 95% CI=-0.62 to -0.05; I²=0%; p<.05) in individuals with neurological disorders. In a sub-analysis by the type of neurological disease, core-based exercises were beneficial only for stroke patients (SMD=-1.05; 95% CI=-2.07 to -0.03; I²=58%; p<.05), but not for those with Parkinson’s disease or chorea. An analysis by the type of core exercise showed that core stability exercises had a significant benefit (SMD=-0.55; 95% CI=-0.97 to -0.14; I²=0%; p<.001), whereas yoga exercises did not demonstrate a significant effect. CONCLUSIONS: In this study, core-based exercises positively improved proprioception in patients with neurological disorders, and were particularly effective in stroke patients. Among various types of core exercises, only core stability exercises had a positive effect on proprioception in patients with neurological disorders