• Biomedical Science Letters
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• v.12 no.4
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• pp.413-418
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• 2006

Charcot-Marie-Tooth disease (CMT) is blown as one of the inherited disorder of peripheral nervous system. Recently, it was found that point mutations in the neurofilament light subunit (NF-L) gene cause CMT. Neurofilaments (NFs) are heteropolymers consist of NF-L, NF-M and NF-H. To assess the relationship between CMT and NF-L mutation in cellular level, we performed phenotypic analysis of the mutant NF-L (E397K) using cultured cell lines. Vimentin-deficient human adrenal carcinoma SW13 (Vim-) cells have a potential to form the intermediate filaments when the cells are expressing both NF-L and NF-M. Our results show that co-expression of wild type NF-L with NF-M showed intermediate filament formation in SW13 (Vim-) cells, while E397K with NF-M did not. This result means that E397K mutant lost its ability to form the intermediate filament in vivo, and further suggests that the E397K mutation is closely related to CMT.

• Proceedings of the Korean Society of Life Science Conference
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• 2006.09a
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• pp.37.2-37.2
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• 2006

• Dementia and Neurocognitive Disorders
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• v.23 no.4
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• pp.188-201
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• 2024

Alzheimer's disease (AD), a leading cause of dementia, presents a formidable global health challenge intensified by the aging population. This review encapsulates the evolving landscape of AD diagnosis and treatment with a special focus on the innovative role of fluid biomarkers. Pathologically, AD is marked by amyloid beta (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau, which lead to synaptic dysfunction, neuronal loss, and cognitive decline. These pathological changes, commencing decades before symptom onset, underscore the need for early detection and intervention. Diagnosis traditionally relies on clinical assessment, neuropsychological testing, and neuroimaging techniques. However, fluid biomarkers in cerebrospinal fluid and blood, such as various forms of Aβ, total tau, phosphorylated tau, and neurofilament light chain, are emerging as less invasive, cost-effective diagnostic tools. These biomarkers are pivotal for early diagnosis, differential diagnosis, disease progression monitoring, and treatment response evaluation. The treatment landscape is shifting toward personalized medicine, highlighted by advancements in Aβ immunotherapies, such as lecanemab and donanemab. Demonstrating efficacy in phase III clinical trials, these therapies hold promise as tailored treatment strategies based on individual biomarker profiles. The integration of fluid biomarkers into clinical practice represents a significant advance in AD management, providing the potential for early and precise diagnosis, coupled with personalized therapeutic approaches. This heralds a new era in combating this debilitating disease.

• Dementia and Neurocognitive Disorders
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• v.21 no.2
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• pp.59-70
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• 2022

Background and Purpose: Neurofilament light chain (NfL) has been considered as a biomarker for neurodegenerative diseases including Alzheimer's disease (AD). We measured plasma NfL levels in older adults with cognitive complaints and evaluated their clinical usefulness in AD. Methods: Plasma levels of NfL, measured by using the single molecule array method, were acquired in a total of 113 subjects consisting of subjective cognitive decline (SCD; n=14), mild cognitive impairment (MCI; n=37), or dementia of Alzheimer type (DAT; n=62). Plasma NfL level was compared among three groups, and its association with cognitive and functional status was also analyzed. Results: After adjusting for age, plasma NfL level was higher in subjects with DAT (65.98±84.96 pg/mL), compared to in subjects with SCD (16.90±2.54 pg/mL) or MCI (25.53±10.42 pg/mL, p=0.004). NfL levels were correlated with scores of the mini-mental state examination (r=-0.242, p=0.021), clinical dementia rating (CDR) (r=0.291, p=0.005), or CDR-sum of boxes (r=0.276, p=0.008). Just for participants who performed amyloid positron emission tomography (PET), the levels were different between subjects with PET (-) (n=17, 25.95±13.25 pg/mL) and PET (+) (n=16, 63.65±81.90 pg/mL, p=0.010). Additionally, plasma NfL levels were different between vascular dementia and vascular MCI, and between Parkinson's disease- dementia and no dementia. Conclusions: This pilot study shows that in subjects with DAT, plasma NfL levels increase. Plasma NfL level correlated with cognitive and functional status. Further longitudinal studies may help to apply the plasma NfL levels to AD, as a potential biomarker for the diagnosis and predicting progression.

• Dementia and Neurocognitive Disorders
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• v.22 no.3
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• pp.109-111
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• 2023

• BMB Reports
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• v.41 no.12
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• pp.868-874
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• 2008

Neurofilaments (NFs) are neuronal intermediate filaments composed of light (NF-L), middle (NF-M), and heavy (NF-H) subunits. NF-L self-assembles into a "core" filament with which NF-M or NF-H co-assembles to form the neuronal intermediate filament. Recent reports show that point mutations of the NF-L gene result in Charcot-Marie-Tooth disease (CMT). However, the most recently described rod domain mutant of human NF-L (A148V) has not been characterized in cellular level. We cloned human NF-L and used it to engineer the A148V. In phenotypic analysis using SW13 cells, A148V mutation completely abolished filament formation despite of presence of NF-M. Moreover, A148V mutation reduced the levels of in vitro self-assembly using GST-NF-L (H/R) fusion protein whereas control (A296T) mutant did not affect the filament formation. These results suggest that alanine at position 148 is essentially required for NF-L self-assembly leading to subsequent filament formation in neuronal cells.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.51-51
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• 2001

Cocaine and amphetamine-regulated transcript (CART) is a satiety factor that is regulated by leptin. It was reported that the mice intracerebroventricularly injected with CART showed behavioral changes resembled with the typical behavioral alterations found in the mice carrying disorders in the brain serotonergic (5-HT) system. Hence, this study was conducted to find out the relationships between CART and 5-HT. We first examined the mRNA levels of CART after the injections of para-chlorophenylalanine (pCPA, 300 mg/kg i.p., single injection or daily for three consecutive days) in the rat brains by in situ hybridization using the mouse CART cDNA probe cloned in our laboratory. Systemic administrations of pCPA, a potent inhibitor of tryptophan hydroxylase, the rate limiting enzyme of 5-HT biosynthesis, acutely depletes the brain 5-HT transporter (5-HTT) in the dorsal raphe nucleus (DRN), which reuptakes terminal 5-HT. Results indicated that the mRNA level of CART significantly decreased in the arcuate nucleus, paraventricular nucleus, and lateral hypothalamic nucleus by three days of daily injection with pCPA with no noticeable change detected 24 hrs after the single injection. The message levels of 5-HTT in DRN decreased in both single and three days of injections. Secondly, to investigate whether CART affect to 5-HT, mouse genomic CART gene, which is consist of 3 exons and 2 introns and mouse neurofilament light (NF-L) chain promoter were cloned. Then, we constructed neuron specific expression vector, which was transfected into HeLa cell using lipid-mediated transfection system. Expression of GFP and CART linked to NF-L-chain promoter in the transfected HeLa cell were detected by using fluorescent microscope and RT-PCR. These results confirmed normal expression of DNA constructs in vitro. Then, to increase brain specific expression of CART in vivo transgenic mice carrying CART gene controlled the deleted NF-L-chain promoter were generated by the DNA microinjection into pronuclei of fertilized embryos. Transgenic mice were detected by Southern blot. Further study is necessary to examine CART expression and 5-HTT in these transgenic mice. Therefore, these results suggest that there maybe a positive molecular correlation between CART and 5-HT in responding to the stimuli.

• Korean Journal of Animal Reproduction
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• v.25 no.4
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• pp.389-397
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• 2001

Cocaine-amphetamine regulated transcript (CART), a satiety factor regulated by leptin, is associated with food intake and motor behavior. In knock out studies, Leu34Phe mutation of human CART gene resulted in obese phenotype but mice carrying a targeted deletion of the CART gene exhibited no dramatic increase of body weight on normal fat diet. To establish a new transgenic mouse model for determining the function of CART on feeding behavior in vivo, we constructed the fusion gene, CART gene under the control of neurofilament light chain promoter, which regulates gene expression at the stage of neuronal differentiation. Transgenic mice were generated by microinjection method and screened by PCR and Southern blot analyses. In these transgenic mice, overexpression of CART was detected by in situ hybridization in spinal cords and brains at 13.5 days post-coitum embryos. At six weeks of age, RT-PCR analysis showed that exogenous CART mRNA was expressed strongly in brains and spinal cords, but not much in other tissues. Our results suggest that these transgenic mice provide a new model to investigate the function of CART gene in neuronal network associated with feeding behavior.