Article
Clinical Neurology
Yiyi Ma, Lei Yu, Marta Olah, Rebecca Smith, Stephanie R. Oatman, Mariet Allen, Ehsan Pishva, Bin Zhang, Vilas Menon, Nilufer Ertekin-Taner, Katie Lunnon, David A. Bennett, Hans-Ulrich Klein, Philip L. De Jager
Summary: Not all individuals carrying the apolipoprotein E (APOE) epsilon 4 gene who survive to old age develop Alzheimer's disease. Factors that can reduce the risk of epsilon 4 on Alzheimer's disease may exist, and one such factor may be associated with a reduced proportion of activated microglia.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Rebecca L. Winfree, Mabel Seto, Logan Dumitrescu, Vilas Menon, Philip De Jager, Yanling Wang, Julie Schneider, David A. Bennett, Angela L. Jefferson, Timothy J. Hohman
Summary: This study investigated the correlation between region-specific TREM2 mRNA expression and neuropathology measures in a large sample size. The results showed that TREM2 expression was related to Alzheimer's disease pathology, cerebrovascular pathology, microglial activation, and cognitive decline, but the associations varied across different brain regions. These findings suggest that TREM2's pathological associations are dependent on the brain region.
ACTA NEUROPATHOLOGICA
(2023)
Review
Biochemistry & Molecular Biology
Oscar M. Munoz M. Herrera, Angela M. M. Zivkovic
Summary: Cholesterol plays a crucial role in brain function and structure, and its dysregulation has been associated with neurodegenerative diseases such as Alzheimer's disease. While the regulation and dysregulation of cholesterol metabolism and transport in neurons and astrocytes are well-studied, less is known about how microglia, the immune cells of the brain, handle cholesterol and how this affects their functions. This review discusses the role of cholesterol in regulating microglia phenotype and function, the effects of statins on microglia, and highlights areas for future research to develop novel therapies for the prevention and treatment of Alzheimer's disease.
Review
Biochemistry & Molecular Biology
Stefania Merighi, Manuela Nigro, Alessia Travagli, Stefania Gessi
Summary: Neuroinflammation may be a crucial avenue for treating and preventing Alzheimer's disease, with microglia playing a key role in the disease process but potentially becoming impaired in later stages. It is important to identify new biomarkers to assess microglial activity and develop novel therapies to restore their physiological function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Oscar Munoz M. Herrera, Brian V. V. Hong, Ulises Ruiz Mendiola, Izumi Maezawa, Lee-Way Jin, Carlito B. Lebrilla, Danielle J. Harvey, Angela M. Zivkovic
Summary: Research has shown that specific genes in microglia are highly associated with Alzheimer's disease (AD) and microglia play a critical role in the development of AD. Therefore, microglia are an important target for novel AD treatment approaches. A study used a multi-stimulant approach to examine the human microglia cell 3 (HMC3) cell line's ability to replicate dysfunctional microglia characteristics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Bartolo Tamburini, Giusto Davide Badami, Marco Pio La Manna, Mojtaba Shekarkar Azgomi, Nadia Caccamo, Francesco Dieli
Summary: The inflammatory response in Alzheimer's disease has both protective and harmful effects. Microglia initially play a protective role but can become overactivated, leading to impaired clearance of β-amyloid peptides and neurodegeneration. Microglia also contribute to the spread of tau pathology. Elevated levels of soluble TREM2 in cerebrospinal fluid are associated with amyloid plaque burden, neurodegeneration, and cognitive decline. Understanding the relationship between innate immunity and Alzheimer's disease could lead to new diagnostic and therapeutic approaches, but further studies are needed for effective treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Eun Sun Jung, Kyujin Suh, Jihui Han, Heyyoung Kim, Hyung-Sik Kang, Won-Seok Choi, Inhee Mook-Jung
Summary: The study reveals that amyloid-beta activates the NLRP3 inflammasome in microglia by activating Syk and inhibiting AMPK, leading to neuroinflammation. Additionally, flufenamic acid (FA), a non-steroidal anti-inflammatory drug, effectively inhibits microglial activation of the NLRP3 inflammasome by regulating Syk and AMPK, offering a potential treatment for AD.
Article
Biochemistry & Molecular Biology
Shiden Solomon, Nirmal Kumar Sampathkumar, Ivo Carre, Mrityunjoy Mondal, George Chennell, Anthony C. Vernon, Marc-David Ruepp, Jacqueline Mitchell
Summary: The rare coding variant PLC gamma 2 (P522R) has been found to protect against late-onset Alzheimer's disease by increasing microglial clearance of amyloid beta and preserving synapses. The variant also leads to alterations in gene expression and mitochondrial function. However, an increased dose of PLC gamma 2 (P522R) can result in reduced beneficial impacts.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Neurosciences
Rebecca Wright
Summary: Disruption of lysosomal signaling leads to increased tau pathology and defective microglia activation.
NATURE NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Amit Pal, Isha Rani, Anil Pawar, Mario Picozza, Mauro Rongioletti, Rosanna Squitti
Summary: This review discusses the involvement of copper in microglia and astrocytes during the course of Alzheimer's disease, providing an updated discussion on the toxicity induced by an imbalance of copper.
Article
Pharmacology & Pharmacy
Berke Karaahmet, John A. Olschowka, M. Kerry O'Banion
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder with strong inflammatory components. However, using glatiramer acetate (GA) to reduce amyloid beta (Aβ) plaque pathology in a mouse model of AD showed only modest decreases in Aβ levels during the development of pathology and unexpectedly increased Aβ levels in later stages. The impact was significant only in female mice and there were no changes in microglial uptake or immune markers on microglia. Caution is needed when repurposing GA for AD treatment.
Review
Biochemistry & Molecular Biology
Carmen Romero-Molina, Victoria Navarro, Sebastian Jimenez, Clara Munoz-Castro, Maria Sanchez-Mico, Antonia Gutierrez, Javier Vitorica, Marisa Vizuete
Summary: Microglia play a critical role in Alzheimer's disease, and different approaches to microglial depletion may simulate various microglial contexts. Previous studies have shown controversial results, mainly due to the heterogeneous and time-varying microglial phenotypes observed in AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xin Yi Choo, Lachlan E. McInnes, Alexandra Grubman, Joanna M. Wasielewska, Irina Belaya, Emma Burrows, Hazel Quek, Jorge Canas Martin, Sanna Loppi, Annika Sorvari, Dzhessi Rait, Andrew Powell, Clare Duncan, Jeffrey R. Liddell, Heikki Tanila, Jose M. Polo, Tarja Malm, Katja M. Kanninen, Paul S. Donnelly, Anthony R. White
Summary: A new copper(II) complex, CuL5, demonstrated anti-neuroinflammatory effects both in vitro and in vivo, potentially offering a new approach for modulating immune function in neurodegenerative diseases. The compound improved cognitive performance in mice models of Alzheimer's disease while also increasing amyloid plaque accumulation, showing promise for further development of copper-based compounds to target neuroinflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Emily Maguire, Georgina E. Menzies, Thomas Phillips, Michael Sasner, Harriet M. Williams, Magdalena A. Czubala, Neil Evans, Emma L. Cope, Rebecca Simss, Gareth R. Howell, Emyr Lloyd-Evans, Julie Williams, Nicholas D. Allen, Philip R. Taylor
Summary: Studies have revealed that the PLC gamma 2-R522 variant may offer protection against Alzheimer's disease (AD) by influencing cellular function, suggesting its potential as a therapeutic target for future treatments.
Review
Medicine, Research & Experimental
Yueran Li, Huifang Xu, Huifang Wang, Kui Yang, Jiajie Luan, Sheng Wang
Summary: Alzheimer's disease is a common neurodegenerative disease that leads to cognitive decline and memory loss. Current treatments only provide symptom relief and do not reverse the disease. Studies have shown that TREM2, predominantly expressed in microglia of the central nervous system, plays a protective role by regulating microglial function and promoting the clearance of toxic substances. However, the specific mechanism of action is not fully understood.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
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
Chemistry, Applied
Eunsoo Yu, Hyungguk Kim, Cheol-Min Park
Summary: The synthesis of heterocycles from 1,2-diarylalkene derivatives through electrosynthesis under metal- and oxidant-free conditions has been discovered. Reactive radical intermediates formed through cathodic reduction or anodic oxidation of specific compounds lead to the formation of various heterocyclic products with good functional group tolerance and high yields. Solvent-dependent chemoselectivity was observed, and mechanistic investigations helped elucidate the reaction mechanisms.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
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
Clinical Neurology
Hee-Jin Kim, YongSoo Shim, Hyun Jeong Han, Byeong C. C. Kim, Kee Hyung Park, So Young Moon, Seong Hye Choi, Dong Won Yang, Bora Yoon, Eun-Joo Kim, Jee Hyang Jeong, Seol-Heui Han
Summary: This study aimed to evaluate the effectiveness of memantine on speech function in patients with moderate to severe Alzheimer's disease who were already on donepezil therapy. The results showed that although the combination therapy was not superior to monotherapy, memantine was still effective in improving behavioral symptoms.
NEUROLOGY AND THERAPY
(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)
Article
Chemistry, Organic
Juyeong Lee, Eunsoo Yu, Cheol-Min Park
Summary: A synthesis method of benzothiophenes through electrosynthesis under oxidant- and metal-free conditions has been discovered, which can efficiently produce benzothiophene compounds with good functional group tolerance.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Clinical Neurology
Hyun Jeong Han, Mee Young Park, Kyung Won Park, Kee Hyung Park, Seong Hye Choi, Hee-Jin Kim, Dong Won Yang, Esther Gunaseli A. P. M. Ebenezer, Yuan-Han Yang, Gurudev M. Kewalram, Seol-Heui Han
Summary: The purpose of this study was to compare the efficacy and safety of the IPI-301 transdermal patch with donepezil tablets in patients with mild-to-moderate Alzheimer's disease (AD). The results showed that IPI-301 was safe and efficacious in improving cognitive function in patients with AD. There were significant differences in the ADCS-ADL scores between the two groups, but no significant differences in the changes of full-itemized ADCS-ADL scores.
JOURNAL OF CLINICAL NEUROLOGY
(2022)
Article
Clinical Neurology
Hee-Jin Kim, Yong S. Shim, Kee Hyung Park, Chan-Nyoung Lee, San Jung, Soo Jin Yoon, Seul-Ki Jeong, Jee Hyang Jeong, Seong Hye Choi, Eun-Joo Kim, Jae-Won Jang, Kyunghun Kang, YoungSoon Yang, SangYun Kim
Summary: The study found that caregiver education did not significantly impact treatment discontinuation rate, but there were significant changes observed in some cognitive tests. Education did not have a significant effect on compliance with donepezil treatment.
JOURNAL OF CLINICAL NEUROLOGY
(2021)