1.YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12
Hongyan ZHOU ; Hae Jin KEE ; Le WAN ; Yodita ASFAHA ; Fabian FISCHER ; Matthias U KASSACK ; Thomas KURZ ; Seong Hoon KIM ; Seung-Jung KEE ; Young Joon HONG ; Myung Ho JEONG
Korean Circulation Journal 2025;55(3):231-247
		                        		
		                        			 Background and Objectives:
		                        			Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. 
		                        		
		                        			Methods:
		                        			New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). 
		                        		
		                        			Results:
		                        			YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. 
		                        		
		                        			Conclusions
		                        			YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway. 
		                        		
		                        		
		                        		
		                        	
2.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
		                        		
		                        			 Background:
		                        			and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. 
		                        		
		                        			Methods:
		                        			Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. 
		                        		
		                        			Results:
		                        			Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. 
		                        		
		                        			Conclusions
		                        			This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management. 
		                        		
		                        		
		                        		
		                        	
3.YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12
Hongyan ZHOU ; Hae Jin KEE ; Le WAN ; Yodita ASFAHA ; Fabian FISCHER ; Matthias U KASSACK ; Thomas KURZ ; Seong Hoon KIM ; Seung-Jung KEE ; Young Joon HONG ; Myung Ho JEONG
Korean Circulation Journal 2025;55(3):231-247
		                        		
		                        			 Background and Objectives:
		                        			Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. 
		                        		
		                        			Methods:
		                        			New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). 
		                        		
		                        			Results:
		                        			YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. 
		                        		
		                        			Conclusions
		                        			YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway. 
		                        		
		                        		
		                        		
		                        	
4.Eligibility for Lecanemab Treatment in the Republic of Korea:Real-World Data From Memory Clinics
Sung Hoon KANG ; Jee Hyang JEONG ; Jung-Min PYUN ; Geon Ha KIM ; Young Ho PARK ; YongSoo SHIM ; Seong-Ho KOH ; Chi-Hun KIM ; Young Chul YOUN ; Dong Won YANG ; Hyuk-je LEE ; Han LEE ; Dain KIM ; Kyunghwa SUN ; So Young MOON ; Kee Hyung PARK ; Seong Hye CHOI
Journal of Clinical Neurology 2025;21(3):182-189
		                        		
		                        			 Background:
		                        			and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. 
		                        		
		                        			Methods:
		                        			We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. 
		                        		
		                        			Results:
		                        			When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. 
		                        		
		                        			Conclusions
		                        			Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education. 
		                        		
		                        		
		                        		
		                        	
5.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
		                        		
		                        			 Background:
		                        			and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. 
		                        		
		                        			Methods:
		                        			Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. 
		                        		
		                        			Results:
		                        			Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. 
		                        		
		                        			Conclusions
		                        			This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management. 
		                        		
		                        		
		                        		
		                        	
6.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
		                        		
		                        			 Background:
		                        			and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. 
		                        		
		                        			Methods:
		                        			Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. 
		                        		
		                        			Results:
		                        			Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. 
		                        		
		                        			Conclusions
		                        			This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management. 
		                        		
		                        		
		                        		
		                        	
7.Eligibility for Lecanemab Treatment in the Republic of Korea:Real-World Data From Memory Clinics
Sung Hoon KANG ; Jee Hyang JEONG ; Jung-Min PYUN ; Geon Ha KIM ; Young Ho PARK ; YongSoo SHIM ; Seong-Ho KOH ; Chi-Hun KIM ; Young Chul YOUN ; Dong Won YANG ; Hyuk-je LEE ; Han LEE ; Dain KIM ; Kyunghwa SUN ; So Young MOON ; Kee Hyung PARK ; Seong Hye CHOI
Journal of Clinical Neurology 2025;21(3):182-189
		                        		
		                        			 Background:
		                        			and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. 
		                        		
		                        			Methods:
		                        			We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. 
		                        		
		                        			Results:
		                        			When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. 
		                        		
		                        			Conclusions
		                        			Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education. 
		                        		
		                        		
		                        		
		                        	
8.YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12
Hongyan ZHOU ; Hae Jin KEE ; Le WAN ; Yodita ASFAHA ; Fabian FISCHER ; Matthias U KASSACK ; Thomas KURZ ; Seong Hoon KIM ; Seung-Jung KEE ; Young Joon HONG ; Myung Ho JEONG
Korean Circulation Journal 2025;55(3):231-247
		                        		
		                        			 Background and Objectives:
		                        			Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. 
		                        		
		                        			Methods:
		                        			New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). 
		                        		
		                        			Results:
		                        			YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. 
		                        		
		                        			Conclusions
		                        			YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway. 
		                        		
		                        		
		                        		
		                        	
9.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
		                        		
		                        			 Background:
		                        			and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. 
		                        		
		                        			Methods:
		                        			Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. 
		                        		
		                        			Results:
		                        			Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. 
		                        		
		                        			Conclusions
		                        			This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management. 
		                        		
		                        		
		                        		
		                        	
10.Eligibility for Lecanemab Treatment in the Republic of Korea:Real-World Data From Memory Clinics
Sung Hoon KANG ; Jee Hyang JEONG ; Jung-Min PYUN ; Geon Ha KIM ; Young Ho PARK ; YongSoo SHIM ; Seong-Ho KOH ; Chi-Hun KIM ; Young Chul YOUN ; Dong Won YANG ; Hyuk-je LEE ; Han LEE ; Dain KIM ; Kyunghwa SUN ; So Young MOON ; Kee Hyung PARK ; Seong Hye CHOI
Journal of Clinical Neurology 2025;21(3):182-189
		                        		
		                        			 Background:
		                        			and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. 
		                        		
		                        			Methods:
		                        			We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. 
		                        		
		                        			Results:
		                        			When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. 
		                        		
		                        			Conclusions
		                        			Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education. 
		                        		
		                        		
		                        		
		                        	
            
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