A5075991846- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Endoplasmic Reticulum Stress and Disease
- Tryptophan and brain disorders
- Autophagy in Disease and Therapy
- Histone Deacetylase Inhibitors Research
- RNA Interference and Gene Delivery
- Natural product bioactivities and synthesis
- Nuclear Receptors and Signaling
- Ion Channels and Receptors
- Amyotrophic Lateral Sclerosis Research
- Autism Spectrum Disorder Research
- Synthesis of Organic Compounds
- Retinoids in leukemia and cellular processes
- Phosphodiesterase function and regulation
- Immune Response and Inflammation
- Neurological disorders and treatments
- Cardiac Fibrosis and Remodeling
- Acupuncture Treatment Research Studies
- Galectins and Cancer Biology
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
Korea Brain Research Institute
2016-2024
University of Helsinki
2020-2024
Biocenter Finland
2020-2023
Kyung Hee University
2010-2021
Sangji University
2007
State University of New York
1998
University of Arkansas for Medical Sciences
1998
The FDA-approved small-molecule drug ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL). Ibrutinib inhibits Bruton's tyrosine kinase (BTK), a involved in B cell receptor signaling. However, the potential regulation of neuroinflammatory responses brain by has not been comprehensively examined. BV2 microglial cells were treated (1 μM) or vehicle (1% DMSO), followed lipopolysaccharide (LPS; 1 μg/ml) PBS. RT-PCR, immunocytochemistry, and subcellular...
Currently there is no neuroprotective or neurorestorative therapy for Parkinson’s disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration dopamine neurons and leads to behavioural recovery through CNTF alpha (CNTFRα) nigral in both MPP+-lesioned adeno-associated virus α-synuclein rat models Western blot immunohistochemical analysis human post-mortem...
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-located protein with cytoprotective effects in neurons and pancreatic β cells vitro models of neurodegeneration diabetes vivo. However, the exact mode MANF action has remained elusive. Here, we show that directly interacts ER transmembrane unfolded response (UPR) sensor IRE1α, identify binding interface between IRE1α. The expression wild-type MANF, but not its IRE1α binding-deficient mutant,...
Abstract Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects motor neurons in the spinal cord, brainstem and cortex, leading to paralysis eventually death within 3–5 years of symptom onset. To date, no cure or effective therapy available. The role chronic endoplasmic reticulum stress pathophysiology amyotrophic sclerosis, as well potential drug target, has received increasing attention. Here, we investigated mode action therapeutic effect reticulum-resident...
Non-invasive delivery of brain therapeutics is a key challenge for treating neurodegenerative diseases. Here, we discovered novel carboxy (C)-terminal fragment cerebral dopamine neurotrophic factor (C-CDNF) that protects (DA) and motoneurons (MNs) in rodent models Parkinsons disease (PD) amyotrophic lateral sclerosis (ALS). C-CDNF retains the same structure as CDNF similarly to regulates cell stress pathways but unorthodoxly enters cultured neurons passes through blood-brain barrier. In...
We demonstrated that capsaicin (CAP), an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), inhibits microglia activation and microglia-derived oxidative stress in the substantia nigra (SN) MPP⁺-lesioned rat. However, detailed mechanisms how is regulated by CAP remain to be determined. Here we report ciliary neurotrophic factor (CNTF) endogenously produced CAP-activated astrocytes through TRPV1, but not microglia, microglial stress, as assessed OX-6 OX-42 immunostaining...
The present study examined whether Aβ(1-42) can induce endogenous expression of interleukin-13 (IL-13) or (IL-4) within activated microglia in the rat hippocampus vivo. We further investigated these cytokines mediate ROS/RNS generation through activation NADPH oxidase and/or inducible nitric oxide synthase (iNOS), and thus contribute to degeneration hippocampal neurons vivo.Here, we show that IL-13 IL-4, endogenously expressed Aβ(1-42)-activated vivo, Neutralization IL-4 protected vivo...
ABSTRACT Human glioblastomas express higher levels of matrix metalloprotease‐2 (MMP‐2) than low‐grade brain tumors and normal tissues. Ascochlorin (ASC) has anti‐metastatic, anti‐angiogenic, synergistic effect in various types cancer cells. However, it remains unknown whether ASC can affect cell migration invasion malignant human glioma In this study, we found that indeed inhibits U373MG A172. significantly suppresses the MMP‐2 gelatinolytic activity expression To determine molecular...
Recent evidence has shown that Ras homolog enriched in brain (Rheb) is dysregulated Alzheimer's disease (AD) brains. However, it still unclear whether Rheb activation contributes to the survival and protection of hippocampal neurons adult brain. To assess effects active vivo, we transfected cornu ammonis 1 (CA1) region normal rats with an adeno-associated virus containing constitutively human (hRheb(S16H)) evaluated on thrombin-induced neurotoxicity. Transduction hRheb(S16H) significantly...
Neuroinflammation is associated with neurodegenerative diseases, including Alzheimer's disease (AD). Thus, modulating the neuroinflammatory response represents a potential therapeutic strategy for treating diseases. Several recent studies have shown that dopamine (DA) and its receptors are expressed in immune cells involved response. we recently developed synthesized non-self-polymerizing analog of DA (CA140) examined effect CA140 on neuroinflammation. To determine effects response, BV2...
Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been proposed as one of the Parkinson's disease (PD) related genes, but possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant that called NT-UCH-L1, in mouse brain tissue NCI-H157 lung cancer SH-SY5Y neuroblastoma cell lines. vivo experiments hydrogen-deuterium exchange (HDX) with tandem mass spectrometry (MS) studies showed NT-UCH-L1 readily...
Cerebral dopamine neurotrophic factor (CDNF) and its close structural relative, mesencephalic astrocyte-derived (MANF), are proteins with properties. CDNF protects restores the function of (DA) neurons in rodent non-human primate (NHP) toxin models Parkinson's disease (PD) therefore shows promise as a drug candidate for disease-modifying treatment PD. Moreover, was found to be safe have some therapeutic effects on PD patients phase 1/2 clinical trials. However, mechanism underlying activity...
Ciliary neurotrophic factor (CNTF) is one of representative factors for the survival dopaminergic neurons. Its effects are primarily mediated via CNTF receptor α (CNTFRα). It still unclear whether levels CNTFRα change in substantia nigra Parkinson's disease (PD) patients, but expression shows remarkable decrease neurons pars compacta (SNpc), suggesting that support CNTF/CNTFRα signaling pathway may be a useful neuroprotective strategy nigrostriatal projection adult brain. Here, we report...
Kyoung In Kim, Jeong Yeob Baek, Jae Yeong Jeong, Jin Han Nam, Eun Su Park, Eugene Bok, Won-Ho Shin, Young Cheul Chung, and Byung Kwan Jin. Exp Neurobiol 2019;28:289-99. https://doi.org/10.5607/en.2019.28.2.289
Background:The accumulation of amyloid-β (Aβ) leads to the loss dendritic spines and synapses, which is hypothesized cause cognitive impairments in Alzheimer's disease (AD) patients. In our previous study, we demonstrated that a novel mercaptoacetamide-based class II histone deacetylase inhib itor (HDACI), known as W2, decreased Aβ levels improved learning memory mice. However, underlying mechanism this effect unknown. Objective:Because spine formation associated with performance, here...
ABSTRACT Histone deacetylase inhibitors (HDACIs) have emerged as potential anticancer agents for the treatment of solid and hematopoietic cancers. Several HDACIs delay cell growth, induce differentiation, or activate apoptosis in multiple types tumors, including glioblastomas. In present study, we showed that mercaptoacetamide‐based HDACI W2 inhibits migration invasion monomorphic malignant human glioma cells. significantly decreased activity expression levels matrix metalloprotease‐2 A172...
Recent studies have shown that Liuwei Dihuang pills (LWPs) can positively affect learning, memory and neurogenesis. However, the underlying molecular mechanisms are not understood. In present study, we developed ALWPs, a mixture of Antler LWPs, investigated whether ALWPs neuroinflammatory responses. We found (500 mg/ml) inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine IL-1β mRNA levels in BV2 microglial cells but primary astrocytes. significantly reduced LPS-induced...
Prothrombin kringle-2 (pKr-2), a domain of prothrombin, can cause the degeneration mesencephalic dopaminergic neurons through microglial activation. However, chemical products that inhibit pKr-2-induced inflammatory activities in brain are still not well known. The present study investigated whether minocycline, semisynthetic tetracycline derivative, could activation and prevent loss nigral (DA) vivo. To address this question, rats were administered unilateral injection pKr-2 substantia...
Multiple sclerosis (MS) is a progressive autoimmune disease characterized by T-cell mediated demyelination in central nervous system (CNS). Experimental encephalomyelitis (EAE) widely used vivo model of MS. Glucocorticoids such as dexamethasone (dex) function immunosuppressants and are commonly to treat acute exacerbations Dex also often positive control EAE studies, it has been shown promote motor behavior, inhibit immune cell infiltration into the CNS regulate activation glial EAE. This...
Abstract N6-Methyladenosine (m6A) is the most common mRNA base modification in eukaryotes. Methylation of adenosine residues to m6A contributes regulation splicing, transport, stability, and translation two main classes enzymes regulate it. The formation catalysed by a methyltransferase complex containing methyltransferase-like 3 (METTL3), METTL14, Wilms’ tumour 1-associated protein (WTAP) as well monomeric METTL16. Demethylation fat mass obesity-associated FTO RNA demethylase AlkB homolog 5...