Stem Cell Therapy for Neurodegenerative Diseases

김승현,이종진,오기욱 한양대학교 의과대학 2015 Hanyang Medical Reviews Vol.35 No.4

Neurodegenerative diseases are the hereditary and sporadic conditions which are characterized by progressive neuronal degeneration. Neurodegenerative diseases are emerging as the leading cause of death, disabilities, and a socioeconomic burden due to an increase in life expectancy. There are many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis, but we have no effective treatments or cures to halt the progression of any of these diseases. Stem cell-based therapy has become the alternative option to treat neurodegenerative diseases. There are several types of stem cells utilized; embryonic stem cells, induced pluripotent stem cells, and adult stem cell (mesenchymal stem cells and neural progenitor cells). In this review, we summarize recent advances in the treatments and the limitations of various stem cell technologies. Especially, we focus on clinical trials of stem cell therapies for major neurodegenerative diseases.

A concise review of human brain methylome during aging and neurodegenerative diseases

( Renuka Prasad G ),( Eek-hoon Jho ) 생화학분자생물학회 2019 BMB Reports Vol.52 No.10

DNA methylation at CpG sites is an essential epigenetic mark that regulates gene expression during mammalian development and diseases. Methylome refers to the entire set of methylation modifications present in the whole genome. Over the last several years, an increasing number of reports on brain DNA methylome reported the association between aberrant methylation and the abnormalities in the expression of critical genes known to have critical roles during aging and neurodegenerative diseases. Consequently, the role of methylation in understanding neurodegenerative diseases has been under focus. This review outlines the current knowledge of the human brain DNA methylomes during aging and neurodegenerative diseases. We describe the differentially methylated genes from fetal stage to old age and their biological functions. Additionally, we summarize the key aspects and methylated genes identified from brain methylome studies on neurodegenerative diseases. The brain methylome studies could provide a basis for studying the functional aspects of neurodegenerative diseases. [BMB Reports 2019; 52(10): 577-588]

Current Updates and Unmet Needs of Brain MRI-Based Artificial Intelligence Software for Patients With Neurodegenerative Diseases in the Republic of Korea

So Yeong Jeong,Chong Hyun Suh,Hwon Heo,Woo Hyun Shim,Sang Joon Kim 대한자기공명의과학회 2022 Investigative Magnetic Resonance Imaging Vol.26 No.4

In aging societies, incidences of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are increasing. Neurodegenerative diseases are bringing main challenges to the healthcare system in today’s world. Analyzing characteristic imaging patterns of patients with neurodegenerative diseases is important. Since objective and reliable imaging assessments and precise analyses can lead to early diagnosis of neurodegenerative diseases, imaging patterns are being increasingly investigated. Artificial intelligence (AI) analyzing brain MRI has been applied to neurodegenerative diseases, providing added value in early diagnosis. MRI-based AI software has been developed and studied worldwide, with some AI-based software already being used in actual clinical care. Currently, there are MRI-based volumetry and segmentation software available. There is also an unmet demand for the application of AI in neurodegenerative diseases. Here, we review current status and unmet needs for application of AI in neurodegenerative diseases. We also discuss current limitations of AI, suggestion for AI-based software, and how it can be clinically applied in the future.

Identification of common therapeutic targets for selected neurodegenerative disorders: An in silico approach

Ahmad, K.,Baig, M.H.,Gupta, G.K.,Kamal, M.A.,Pathak, N.,Choi, I. Elsevier 2016 Journal of computational science Vol.17 No.1

<P>Neurodegenerative disorders (NDs) are a heterogeneous group of disorders generally characterized by a profound decrease in the size and volume of the human brain due to death of neurons. These disorders include a variety of progressive disorders that result in cognitive and/or motor degradation. The present study was conducted to identify common potential targets for multi-neurodegenerative diseases. To accomplish this, we have selected six common neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Prion disease and Dentatorubral-pallidoluysian atrophy (DRPLA) for identification of common regulatory target proteins. A total of sixteen common proteins were identified as target proteins by disease pathway analysis and previous studies based on their association with more than two NDs, including AD. An interaction network of each of the sixteen target proteins was then constructed against causative proteins selected from all six NDs by using the STRING 9.1 program. Pathway analysis and the protein-protein interaction network suggested that CASP-3 and CASP-8 were associated with the maximum number of selected NDs and may therefore be the most potent target proteins for, treatment of multi-neurodegenerative diseases. (C) 2016 Elsevier B.V. All rights reserved.</P>

퇴행성 뇌질환에서 뇌 자기공명영상 기반 인공지능 소프트웨어 활용의 현재

So Yeong Jeong,Chong Hyun Suh,Ho Young Park,Hwon Heo,Woo Hyun Shim,Sang Joon Kim 대한영상의학회 2022 대한영상의학회지 Vol.83 No.3

The incidence of neurodegenerative diseases in the older population has increased in recent years. A considerable number of studies have been performed to characterize these diseases. Imaging analysis is an important biomarker for the diagnosis of neurodegenerative disease. Objective and reliable assessment and precise detection are important for the early diagnosis of neurodegenerative diseases. Artificial intelligence (AI) using brain MRI applied to the study of neurodegenerative diseases could promote early diagnosis and optimal decisions for treatment plans. MRI-based AI software have been developed and studied worldwide. Representatively, there are MRI-based volumetry and segmentation software. In this review, we present the development process of brain volumetry analysis software in neurodegenerative diseases, currently used and developed AI software for neurodegenerative disease in the Republic of Korea, probable uses of AI in the future, and AI software limitations.

Amyloid beta plaque accumulation and memory function decline exacerbated by SAA1 in Alzheimer’s disease

Ji Won Ko,Zae Young Ryoo,Myoung Ok Kim 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Neurodegenerative diseases like Parkinson’s disease (PD), Alzheimer’s diseases (AD) could be occurred from numerous reasons which result in neuronal death. Inflammation has been also regarded as one of the major causes of neurodegenerative disorders. In this respect, Serum amyloid A1 (SAA1) which is highly expressed in patients who have neurodegenerative disease implies that it takes some part in neurodegenerative disorders. SAA1 aggravates neuronal inflammation even though it is not an initiator of neuronal damage. Our previous studies revealed that liver-derived SAA1 aggregated in the brain by crossing the brain-blood barrier (BBB) present depressive-like behavior on mouse when it is overexpressing. However, it did not disclose how SAA1 regulates brain functions and why neurodegenerative patients show increasing pattern of SAA1. Therefore, we wondered the effects of SAA1 overexpression in neurodegenerative mouse model, and focused on the neuronal inflammation in Alzheimer’s disease. Especially, we established APP/SAA over-expressed double transgenic mice that both over-expressing amyloid precursor protein (APP)-c105 and SAA1 based on the Alzheimer"s disease (AD) research which has historically used transgenic (Tg) mouse models that overexpress mutant amyloid precursor protein (APP). With using this APP/SAA1 mice for scrutinizing the roles of SAA1 in the brain, we revealed that SAA1 overexpression brings about amyloid beta (Aβ) accumulation, glial activation, and memory decline. In other words, SAA1 overexpression increases neuroinflammation by making abundant amyloid beta in in the brain and trigger Alzheimer’s disease in the end.

Natural products and their active principles used in the treatment of neurodegenerative diseases: a review

Mehnaz Kamal,Mamuna Naz,Talha Jawaid,Muhammad Arif 경희대학교 융합한의과학연구소 2019 Oriental Pharmacy and Experimental Medicine Vol.19 No.4

Free radicals are the byproducts of physiological aerobic cellular metabolism. Intrinsic antioxidant system plays its pivotal function in prevention of any loss due to free radicals. Though, incorporation or excess production of free radicals from environment to living system or imbalanced defense mechanism of antioxidant system leads to severe consequences like neuro-degeneration. Sensory or functional loss occurs in neural cells in neurodegenerative diseases. Besides numerous other genetic or environmental factors, oxidative stress is the major cause which leads to damage of neurons and production of neurodegenative diseases. However, oxygen is vital for existence, excessive reactive oxygen species production and imbalanced metabolism leads to a variety of diseases such as aging, Parkinson’s disease, Alzheimer’s disease, and many other neurodegenative diseases. Free radicals toxicity contributes to DNA and proteins damage, tissue damage, infammation and consequent cellular apoptosis. Neuroprotection is a broad term commonly used to refer therapeutic strategies that can prevent, delay or even reverse neuronal damage. Since thousands of years, lots of medicinal plants have been used in a group of herbal preparations of Ayurveda (Indian traditional health care system) named Rasayana because of the antioxidant principles present in it, responsible for their medicinal use in neurodegenerative diseases. This work constitutes a literature review on natural products contain antioxidant principles used in the treatment of neurodegenerative disease.

Epigenetic Changes in Neurodegenerative Diseases

이성배,Min Jee Kwon,Sunhong Kim,Myeong Hoon Han 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.11

Afflicted neurons in various neurodegenerative diseases generally display diverse and complex pathological fea-tures before catastrophic occurrence of massive neuronal loss at the late stages of the diseases. This complex nature of neuronal pathophysiology inevitably implicates systemwide changes in basic cellular activities such as transcriptional controls and signal cascades, and so on, as a cause. Recently, as one of these systemwide cellular changes associated with neurodegenerative diseases, epigenetic changes caused by protein toxicity have begun to be highlighted. Notably, recent advances in related techniques including next-generation sequencing (NGS) and mass spectrometry enable us to monitor changes in the post-translational modifications (PTMs) of histone proteins and to link these changes in histone PTMs to the specific transcriptional changes. Indeed, epigenetic alterations and consequent changes in neuronal transcriptome are now begun to be extensively studied in neurodegener-ative diseases including Alzheimer’s disease (AD). In this review, we will discuss details of our current understand-ings on epigenetic changes associated with two repre-sentative neurodegenerative diseases [AD and polygluta-mine (polyQ) diseases] and further discuss possible future development of pharmaceutical treatment of the diseases through modulating these epigenetic changes.

Pharmacological intervention of early neuropathy in neurodegenerative diseases

Kwon, Min Jee,Kim, Jeong-Hoon,Kim, TaeSoo,Lee, Sung Bae Elsevier 2017 PHARMACOLOGICAL RESEARCH Vol.119 No.-

<P><B>Abstract</B></P> <P>Extensive studies have reported the significant roles of numerous cellular features and processes in properly maintaining neuronal morphology and function throughout the lifespan of an animal. Any alterations in their homeostasis appear to be strongly associated with neuronal aging and the pathogenesis of various neurodegenerative diseases, even before the occurrence of prominent neuronal death. However, until recently, the primary focus of studies regarding many neurodegenerative diseases has been on the massive cell death occurring at the late stages of disease progression. Thus, our understanding on early neuropathy in these diseases remains relatively limited. The complicated nature of various neuropathic features manifested early in neurodegenerative diseases suggests the involvement of a system-wide transcriptional regulation and epigenetic control. Epigenetic alterations and consequent changes in the neuronal transcriptome are now begun to be extensively studied in various neurodegenerative diseases. Upon the catastrophic incident of neuronal death in disease progression, it is utterly difficult to reverse the deleterious defects by pharmacological treatments, and therefore, therapeutics targeting the system-wide transcriptional dysregulation associated with specific early neuropathy is considered a better option. Here, we review our current understanding on the system-wide transcriptional dysregulation that is likely associated with early neuropathy shown in various neurodegenerative diseases and discuss the possible future developments of pharmaceutical therapeutics.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Roles of chitinase 3-like 1 in the development of cancer, neurodegenerative diseases, and inflammatory diseases

Yeo, In Jun,Lee, Chong-Kil,Han, Sang-Bae,Yun, Jaesuk,Hong, Jin Tae Elsevier 2019 Pharmacology & therapeutics Vol.203 No.-

<P><B>Abstract</B></P> <P>Chitinase 3-like 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 is strongly increased by various inflammatory and immunological conditions, including rheumatoid arthritis, multiple sclerosis, Alzheimer’s disease, and several cancers. However, its physiological and pathophysiological roles in the development of cancer and neurodegenerative and inflammatory diseases remain unclear. Several studies have reported that CHI3L1 promotes cancer proliferation, inflammatory cytokine production, and microglial activation, and that multiple receptors, such as advanced glycation end product, syndecan-1/αVβ3, and IL-13Rα2, are involved. In addition, the pro-inflammatory action of CHI3L1 may be mediated via the protein kinase B and phosphoinositide-3 signaling pathways and responses to various pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon-γ. Therefore, CHI3L1 could contribute to a vast array of inflammatory diseases. In this article, we review recent findings regarding the roles of CHI3L1 and suggest therapeutic approaches targeting CHI3L1 in the development of cancers, neurodegenerative diseases, and inflammatory diseases.</P>