Article
Environmental Sciences
Xiaozheng Zhu, Huiping Liu, Diya Wang, Ruili Guan, Yuankang Zou, Ming Li, Jianbin Zhang, Jingyuan Chen
Summary: As more and more people move to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment have attracted public attention, but the underlying mechanisms are still unclear. Emerging evidence suggests that neuroinflammation and neuronal loss may be involved. In this study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our results showed that hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, accompanied by neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Furthermore, we used NLRP3 knockout mice to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Cell Biology
Hongwei Wang, Wei Xiong, Sitong Hang, Yanmin Wang, Sisen Zhang, Song Liu
Summary: This study investigated the precise mechanism underlying cognitive decline after IH insult, revealing that SENP1 downregulation could exacerbate inflammation and neuronal apoptosis, further reducing the level of PPARγ. However, the application of PPARγ agonist could suppress the enhancement of inflammation and neuronal apoptosis. Behavioral experiments in IH mice showed that SENP1 downregulation worsened cognitive impairment.
Article
Neurosciences
Yun Fan, Mei-Chuan Chou, Yen-Chin Liu, Ching-Kuan Liu, Chu-Huang Chen, Shiou-Lan Chen
Summary: Sleep apnea disrupts physiological homeostasis and can lead to neuronal dysfunction and anxiety, without significant impact on cognitive function. Chronic intermittent hypoxia alters synaptic plasticity in the brain, resulting in anxiety-like behaviors in mice. Treatment with NMDA receptor antagonist attenuates anxiety-like behavior induced by chronic IH, suggesting early intervention is important in managing anxiety-related complications in sleep apnea patients.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Cell Biology
Hongwei Wang, Tianyun Yang, Jinyuan Sun, Sisen Zhang, Song Liu
Summary: The study found that SENP1 regulates neuroinflammation induced by IH by modulating the SUMOylation of NEMO, activating the NF-kappa B pathway and affecting cognition. Targeting SENP1 may represent a novel therapeutic strategy for IH-induced cognitive decline.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Neurosciences
Huiya Ying, Zilong Zhang, Wei Wang, Zijing Yang, Cancan You, Yuanai Li, Xiaohong Cai, Xiucui Li
Summary: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by chronic intermittent hypoxia (CIH) and cognitive dysfunction in children. In this study, the role of calcium-sensing receptor (CaSR) in CIH-induced memory dysfunction was investigated. CIH exposure led to cognitive dysfunction, hippocampal neuronal apoptosis, and synaptic plasticity deficit in mice. Inhibition of CaSR alleviated these effects in the hippocampus. Additionally, activation of CaSR accelerated CIH-induced apoptosis and synaptic plasticity deficit in PC12 cells.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Sourin Bhuniya, Manish Goyal, Nilotpal Chowdhury, Priyadarshini Mishra
Summary: Patients with obstructive sleep apnea have higher serum levels of amyloid-beta and tau proteins, which are associated with nocturnal oxygen saturation and changes in sleep architecture. Monitoring for signs of cognitive impairment and treating obstructive sleep apnea may reverse neurodegenerative changes and prevent cognitive impairment.
JOURNAL OF SLEEP RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Xuan Xu, Peng-Hao Zhen, Fu-Chao Yu, Tao Wang, Sheng-Nan Li, Qin Wei, Jia-Yi Tong
Summary: Obstructive sleep apnea (OSA) accelerates the progression of chronic heart failure (CHF). Mechanistic experiments showed that chronic intermittent hypoxia (CIH) exposure activates HIF-1 alpha and miR-29c, inhibiting SERCA2a expression and promoting cardiac dysfunction and remodeling. Overexpression of PHD3 alleviates CIH-induced cardiac dysfunction and remodeling by stabilizing SERCA2a expression.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Psychology, Biological
Li Zhao, Lei Zhang, Wei Zhu, Hongguang Chen, Yuexia Ding, Guangqiang Cui
Summary: The miR-203 inhibitor treatment in TBI mice showed promising results in protecting against neural damage and improving cognitive and motor function by inhibiting tau phosphorylation, ApoE4 expression, and neuronal apoptosis.
PHYSIOLOGY & BEHAVIOR
(2021)
Article
Immunology
Hongwei Wang, Xu Wang, Yubin Shen, Yanmin Wang, Tianyun Yang, Jinyuan Sun, Song Liu
Summary: Chronic intermittent hypoxia (CIH) is a characteristic pathological change of obstructive sleep apnea syndrome (OSAS). Inflammation of microglia induced by CIH plays a crucial role in OSAS-associated cognitive dysfunction. SUMO-specific proteases 1 (SENP1) has been implicated in tumor inflammatory microenvironment and cell migration, but its role in CIH-induced neuroinflammation is still unknown.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Richa Choudhary, Mukesh Kumar, Anju Katyal
Summary: This study investigates the mechanism of action of 12/15 lipoxygenase in high altitude cerebral edema and reveals its involvement in disruption of mitochondrial integrity and neuronal apoptosis, suggesting it as a potential therapeutic target.
Article
Biochemistry & Molecular Biology
Byung Jo Choi, Kang Ho Park, Min Hee Park, Eric Jinsheng Huang, Seung Hyun Kim, Jae-sung Bae, Hee Kyung Jin
Summary: Studies have shown that increased activity of acid sphingomyelinase (ASM) is observed in both ALS patients and mouse models. Genetic inhibition of ASM can improve symptoms and reduce spinal neuronal loss in an ALS mouse model. These findings suggest that ASM may be an effective therapeutic target for ALS.
Article
Cell Biology
Lee J. Martin, Mark V. Niedzwiecki, Margaret Wong
Summary: Therapeutic hypothermia was found to delay disease onset and reduce functional decline in a transgenic mouse model of ALS. Cooling had protective effects in the CNS and skeletal muscle, targeting mitochondria and extending lifespan in ALS mice.
Article
Biochemistry & Molecular Biology
Wenxin Tang, Yansong Li, Shuxuan He, Tao Jiang, Nan Wang, Mengyu Du, Bo Cheng, Wei Gao, Yan Li, Qiang Wang
Summary: This study suggests that ferroptosis promotes the progression of diabetes-associated cognitive dysfunction (DACD) and supports the correlation between ferroptosis and DACD in type 2 diabetes mellitus (T2DM). The results provide new insights into the potential antioxidant effects of ferroptosis inhibitors and cav-1 on DACD.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Review
Biochemistry & Molecular Biology
Kazuhide Asakawa, Hiroshi Handa, Koichi Kawakami
Summary: TDP-43 is an evolutionarily conserved hnRNP encoded by the TARDBP gene, which plays a crucial role in regulating RNA metabolism in ALS. Studies using cellular and animal models have provided insights into potential links between TDP-43 and the vulnerability of motor neurons in ALS.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Neurosciences
Karim S. Ibrahim, Salah El Mestikawy, Khaled S. Abd-Elrahman, Stephen S. G. Ferguson
Summary: Huntington's disease (HD) is a neurodegenerative disease characterized by motor and cognitive impairments. The role of vesicular glutamate transporter-3 (VGLUT3) in HD pathophysiology is unclear. This study found that VGLUT3 deletion rescued motor and cognitive deficits in HD mouse models, likely through the activation of Akt and ERK1/2 pathways. These findings suggest that VGLUT3 could be a potential target for HD therapeutics.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Ju Youn Lee, Seung Hoon Han, Min Hee Park, Im-Sook Song, Min-Koo Choi, Eunsoo Yu, Cheol-Min Park, Hee-Jin Kim, Seung Hyun Kim, Edward H. Schuchman, Hee Kyung Jin, Jae-sung Bae
NATURE COMMUNICATIONS
(2020)
Article
Psychiatry
Andrea Vergallo, Simone Lista, Yuhai Zhao, Pablo Lemercier, Stefan J. Teipel, Marie-Claude Potier, Marie-Odile Habert, Bruno Dubois, Walter J. Lukiw, Harald Hampel
Summary: The study identified brain-enriched miRNAs in a cohort of cognitively normal individuals with subjective memory complaints. It investigated the impact of age, sex, and the APOE epsilon 4 allele on miRNA plasma concentrations and explored associations with brain metabolic uptake using PET imaging. The results suggest potential associations between miRNA concentrations and neuroimaging biomarkers of AD pathophysiology.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Cell Biology
Wan Yun Ho, Jer-Cherng Chang, Kenneth Lim, Amaury Cazenave-Gassiot, Aivi T. Nguyen, Juat Chin Foo, Sneha Muralidharan, Ashley Viera-Ortiz, Sarah J. M. Ong, Jin Hui Hor, Ira Agrawal, Shawn Hoon, Olubankole Aladesuyi Arogundade, Maria J. Rodriguez, Su Min Lim, Seung Hyun Kim, John Ravits, Shi-Yan Ng, Markus R. Wenk, Edward B. Lee, Greg Tucker-Kellogg, Shuo-Chien Ling
Summary: The protein TDP-43 influences cholesterol metabolism in oligodendrocytes by directly binding to mRNA of key regulators. Depletion of TDP-43 leads to reduced expression of SREBF2 and LDLR, resulting in lower cholesterol levels. Reintroducing SREBF2 or LDLR can reverse the effects of TDP-43 depletion on cholesterol levels.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Harald Hampel, John Hardy, Kaj Blennow, Christopher Chen, George Perry, Seung Hyun Kim, Victor L. Villemagne, Paul Aisen, Michele Vendruscolo, Takeshi Iwatsubo, Colin L. Masters, Min Cho, Lars Lannfelt, Jeffrey L. Cummings, Andrea Vergallo
Summary: Breakthroughs in molecular medicine have highlighted the significance of the amyloid-beta pathway in the pathophysiology of Alzheimer's disease. Established biochemical alterations of the A beta cycle serve as promising targets for the development of disease-modifying therapies. Research indicates a crucial role of A beta pathway dyshomeostasis in the dynamics of AD pathophysiology, supporting the development of A beta-targeting therapeutic strategies for early treatment of AD.
MOLECULAR PSYCHIATRY
(2021)
Editorial Material
Clinical Neurology
Kristiana Salmon, Matthew C. Kiernan, Seung H. Kim, Peter M. Andersen, Adriano Chio, Leonard H. van den Berg, Philip Van Damme, Ammar Al-Chalabi, Patricia Lillo, Jinsy A. Andrews, Angela Genge
Article
Multidisciplinary Sciences
Min Hee Park, Kang Ho Park, Byung Jo Choi, Wan Hui Han, Hee Ji Yoon, Hye Yoon Jung, Jihoon Lee, Im-Sook Song, Dong Yu Lim, Min-Koo Choi, Yang-Ha Lee, Cheol-Min Park, Ming Wang, Jihoon Jo, Hee-Jin Kim, Seung Hyun Kim, Edward H. Schuchman, Hee Kyung Jin, Jae-Sung Bae
Summary: Alzheimer's disease (AD) is a complex neurodegenerative disorder. KARI 201, identified as both an ASM inhibitor and a ghrelin receptor agonist, has shown potential in rescuing neuropathological features and improving memory function in AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Jinsup Kim, Won Hyuk Lee, Seung Hyun Kim, Jae Yoon Na, Young-Hyo Lim, Seok Hyun Cho, Sung Ho Cho, Hyun-Kyung Park
Summary: This study demonstrated that utilizing the impulse-radio ultrawideband (IR-UWB) radar sensor technique can provide accurate estimates of anthropometric parameters, highly consistent with bioelectrical impedance analysis (BIA) results.
SCIENTIFIC REPORTS
(2022)
Article
Nutrition & Dietetics
Jihyun Eom, Bugyeong Son, Seung Hyun Kim, Yongsoon Park
Summary: Intake of antioxidants, especially those derived from vegetables and legumes, has a beneficial effect on delaying disease progression and prolonging survival in patients with ALS.
Article
Clinical Neurology
Hyuk Sung Kwon, Yeonjae Park, Ji Hyun Kim, Seung Hyun Kim, Jae-Bum Jun, Sojeong Park, Dae Ryong Kang, Hojin Choi
Summary: This study investigated the prevalence of motor neuron diseases (MNDs) in gout patients and found that gout may have a protective effect against the risk of MNDs. The prevalence of MNDs, especially amyotrophic lateral sclerosis (ALS), was significantly lower in gout patients compared to the general population.
NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Young Nam Kwon, Mark Woodhall, Jung-Joon Sung, Kwang-Kuk Kim, Young-Min Lim, Hyunjin Kim, Jee-Eun Kim, Seol-Hee Baek, Byung-Jo Kim, Jin-Sung Park, Hung Youl Seok, Dae-Seong Kim, Ohyun Kwon, Kee Hong Park, Eunhee Sohn, Jong Seok Bae, Byung-Nam Yoon, Nam-Hee Kim, Suk-Won Ahn, Kyomin Choi, Jeeyoung Oh, Hyung Jun Park, Kyong Jin Shin, Sanggon Lee, Jinseok Park, Seung Hyun Kim, Jung Im Seok, Dae Woong Bae, Jae Young An, In Soo Joo, Seok-Jin Choi, Tai-Seung Nam, Sunyoung Kim, Ki-Jong Park, Ki-Han Kwon, Patrick Waters, Yoon-Ho Hong
Summary: This study aimed to evaluate the diagnostic accuracy of ELISA for anti-MuSK antibody in AChR antibody-negative generalized MG patients and investigate the clinical contexts for the diagnosis of MuSK MG. The results showed that the positive results of ELISA were mostly consistent with CBA and RIPA. The most common differential diagnosis was motor neuron disease. These findings are of great importance for the diagnosis of MuSK MG in clinical practice.
JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Min-Young Noh, Min-Soo Kwon, Ki-Wook Oh, Minyeop Nahm, Jinseok Park, Young-Eun Kim, Chang-Seok Ki, Hee Kyung Jin, Jae-sung Bae, Seung Hyun Kim
Summary: This study identified a key factor, microglial NCKAP1, that is associated with the functional characteristics and progression of rapidly progressive sporadic ALS. ALS patients with rapid progression showed defective phagocytosis and an exaggerated pro-inflammatory response in microglia. Decreased NCKAP1 expression in microglia was correlated with the progression of ALS, suggesting that it may be a potential therapeutic target.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Wonjae Sung, Hyuk Sung Kwon, Yeonjae Park, Seung Hyun Kim, Sojeong Park, Dae Ryong Kang, Hojin Choi
Summary: This study analyzed the prevalence of dementia among patients diagnosed with gout in South Korea and found a relatively low prevalence of dementia in patients with gout. The study also found that patients with both gout and dementia were more likely to be women, have a wide range of comorbidities, and be prescribed gout-related medications.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Multidisciplinary Sciences
Wan Yun Ho, Li-Ling Chak, Jin-Hui Hor, Fujia Liu, Sandra Diaz-Garcia, Jer-Cherng Chang, Emma Sanford, Maria J. Rodriguez, Durgadevi Alagappan, Su Min Lim, Yik-Lam Cho, Yuji Shimizu, Alfred Xuyang Sun, Sheue-Houy Tyan, Edward Koo, Seung Hyun Kim, John Ravits, Shi-Yan Ng, Katsutomo Okamura, Shuo-Chien Ling
Summary: In this study, researchers analyzed the miRNA repertoires in spinal cords and hippocampi from ALS-FUS mice to understand the role of FUS-dependent miRNA deregulation in ALS. They identified differentially expressed miRNAs between CNS regions and disease states. One up-regulated miRNA, miR-1197, was found to target the pro-survival pseudokinase Trib2. They also observed reduced TRIB2 expression in motor neurons derived from ALS patients. Stabilizing TRIB2 protein with a cancer drug improved the survival of human motor neurons, including those from a sporadic ALS patient. These findings suggest that profiling miRNAs can help uncover the molecular mechanisms underlying selective vulnerability in ALS, and TRIB2 may be a potential therapeutic target.
Review
Clinical Neurology
Su Min Lim, Minyeop Nahm, Seung Hyun Kim
Summary: The balance of proteins and RNA is crucial for maintaining brain structure and function, but aging, cellular stress, and genetic factors can disrupt this balance, leading to protein misfolding, aggregate deposition, and abnormal dynamics of ribonucleoprotein granules. These disruptions contribute to age-related neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS. The formation of pathogenic aggregates, including tau and alpha-synuclein, is linked to irreversible liquid-liquid phase separation (LLPS), suggesting chaperone/disaggregase as potential therapeutic targets. This review emphasizes the importance of understanding cell death mechanisms and ribostasis in diseases.
JOURNAL OF CLINICAL NEUROLOGY
(2023)
Letter
Clinical Neurology
Wonjae Sung, Young-Eun Kim, Seung Hyun Kim
JOURNAL OF CLINICAL NEUROLOGY
(2021)