Article
Neurosciences
Philip Regan, Katriona L. Hole, Julia Sero, Robert J. Williams
Summary: Microglia play a crucial role in late-onset Alzheimer's disease, and flavanol 3-ols have the potential to modulate microglial responsiveness and be used therapeutically.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Geriatrics & Gerontology
Jifei Miao, Haixia Ma, Yang Yang, Yuanpin Liao, Cui Lin, Juanxia Zheng, Muli Yu, Jiao Lan
Summary: This review summarizes the crucial role of microglia in the pathogenesis of Alzheimer's disease (AD), including genetic determinants, phenotypic state, phagocytic capacity, neuroinflammatory response, and impact on synaptic plasticity and neuronal regulation. Furthermore, it discusses recent developments in drug discovery targeting microglia in AD, highlighting potential avenues for therapeutic intervention. This review emphasizes the essential role of microglia in AD and provides insights into potential treatments.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Lee-Way Jin, Jacopo Di Lucente, Ulises Ruiz Mendiola, Nopparat Suthprasertporn, Alexey Tomilov, Gino Cortopassi, Kyoungmi Kim, Jon J. Ramsey, Izumi Maezawa
Summary: This study investigated the impact of BHB on AβO-stimulated hiMG and found that BHB can mitigate inflammation and mitochondrial damage caused by AβO, rectify MKP, and restore cellular function. The authors suggest that these effects of BHB may contribute to the therapeutic benefits of ketogenic diet intervention in aged mice and individuals with mild AD.
Article
Chemistry, Multidisciplinary
Shiuan-Haur Su, Yujing Song, Michael W. Newstead, Tao Cai, MengXi Wu, Andrew Stephens, Benjamin H. Singer, Katsuo Kurabayashi
Summary: The digital Phenoplate (dPP) is an integrated platform that allows ultra-sensitive measurement of cellular cytokine secretory profiles, making it suitable for high precision and high throughput characterization of cellular phenotypes.
Article
Neurosciences
Anna A. Pimenova, Manon Herbinet, Ishaan Gupta, Saima I. Machlovi, Kathryn R. Bowles, Edoardo Marcora, Alison M. Goate
Summary: The study demonstrates that PU.1 expression levels in microglia modulate various microglial responses, with increased expression associated with heightened pro-inflammatory response related to increased cell viability under cytotoxic conditions. On the other hand, low expression of PU.1 leads to increased cell death under cytotoxic conditions and reduced pro-inflammatory signaling, highlighting the protective effect of SPI1 genotype in Alzheimer's disease.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Clinical Neurology
Xianwei Wang, Lu Liu, Xiaohua Jiang, Jason Saredy, Hang Xi, Ramon Cueto, Danni Sigler, Mohsin Khan, Sheng Wu, Yong Ji, Nathaniel W. Snyder, Wenhui Hu, Xiaofeng Yang, Hong Wang
Summary: This study investigated the effect of hyperhomocysteinemia (HHcy) on the phagocytosis of amyloid beta (A beta) by microglia (MG) in Alzheimer's disease (AD). Transcriptome analysis revealed that HHcy suppressed A beta phagocytosis by MG and identified key genes involved in this process.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Cell Biology
Marva Lachish, Nina Fainstein, Tal Ganz, Lihi Sofer, Tamir Ben-Hur
Summary: Brain neural precursor cells (NPCs) support microglial function to clear excess amyloid beta (Aβ), but NPC from the Alzheimer's disease (AD) environment fail to do so, potentially accelerating disease pathology.
Article
Biochemistry & Molecular Biology
Yu-Kai Huang, Chia-Chun Liu, Shining Wang, Hui-Chun Cheng, Chandler Meadows, Kun-Che Chang
Summary: The occurrence of Alzheimer's disease is associated with the accumulation of beta-amyloid plaques, which activate microglia and lead to neuroinflammation. In this study, the role of aldose reductase (AR) in beta-amyloid-induced inflammation and neuronal death was investigated. AR inhibition was found to attenuate reactive oxygen species and tumor necrosis factor alpha secretion in microglia, as well as reduce their phagocytotic capability and cell migration. Co-culturing beta-amyloid-induced microglia with neurons also showed that AR inhibition protected against neuronal damage. These findings highlight AR regulation as a potential therapeutic target for Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Yuanxin Zhao, Buhan Liu, Jian Wang, Long Xu, Sihang Yu, Jiaying Fu, Xiaoyu Yan, Jing Su
Summary: Neuroinflammation mediated by microglia is a common feature in neurodegenerative diseases. The accumulation of Aβ and tau proteins can disrupt the metabolism of microglia, leading to neuroinflammation.
Article
Cell Biology
Jianing Wang, Xiaoying Qin, Hao Sun, Meijun He, Qunyu Lv, Congcong Gao, Xinran He, Hong Liao
Summary: The study shows that NgR plays a crucial role in microglial clearance of Aβ, with increased NgR expression in aged microglia leading to decreased Aβ phagocytosis. Knockdown of NgR reduces amyloid burden and improves cognitive function in an AD mouse model. Moreover, NgR activation inhibits CD36 gene expression through Smad2/3 signaling, thereby reducing microglial Aβ uptake.
Article
Multidisciplinary Sciences
Hannah Ennerfelt, Coco Holliday, Daniel A. Shapiro, Kristine E. Zengeler, Ashley C. Bolte, Tyler K. Ulland, John R. Lukens
Summary: Recent advances have shown the importance of microglia-expressed innate immune receptors in Alzheimer's disease (AD), specifically TREM2, CD33, and CD22. However, the downstream signaling molecules used by these receptors in AD are still not well understood. This study demonstrates that CARD9, an intracellular adaptor molecule, plays a crucial role in A(3-mediated disease and microglial responses in AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
Neurosciences
Izabela Lepiarz-Raba, Ismail Gbadamosi, Roberta Florea, Rosa Chiara Paolicelli, Ali Jawaid
Summary: Microglia, the resident immune cells of the brain, play a crucial role in regulating brain health and disease. The functions of microglia are closely related to their metabolism, providing an opportunity to modulate their activities through nutritional or metabolic interventions. In Alzheimer's disease, enhancing microglial phagocytosis of amyloid beta aggregates by metabolic interventions may have therapeutic potential.
TRANSLATIONAL NEURODEGENERATION
(2023)
Article
Geriatrics & Gerontology
Chih-Yuan Ko, Jian-Hua Xu, Yu-Wei Chang, Yangming Martin Lo, James Swi-Bea Wu, Wen-Chung Huang, Szu-Chuan Shen
Summary: This study demonstrated that ALA enhances the phagocytosis of oA beta(1-42) in BV-2 cells by upregulating the COX-2/15-deoxy-(& UDelta;12,14)-prostaglandin J2/PPAR-gamma/CD36 pathway. Future studies should validate these findings with in vivo studies.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Plant Sciences
Min-Ji Jung, Namkwon Kim, Seung Ho Jeon, Min Sung Gee, Ji-Woon Kim, Jong Kil Lee
Summary: The study investigated the effects of eugenol on Alzheimer's disease (AD) and found that eugenol effectively improved cognitive function and reduced pathological changes in 5xFAD mice. The underlying mechanisms may involve inhibiting neuronal cell death and promoting beta-amyloid clearance.
Article
Neurosciences
Henna Konttinen, Irina Gureviciene, Minna Oksanen, Alexandra Grubman, Sanna Loppi, Mikko T. Huuskonen, Paula Korhonen, Riikka Lampinen, Meike Keuters, Irina Belaya, Heikki Tanila, Katja M. Kanninen, Gundars Goldsteins, Gary Landreth, Jari Koistinaho, Tarja Malm
Article
Neurosciences
Dilyara Nurkhametova, Igor Kudryavtsev, Valeriia Guselnikova, Maria Serebryakova, Raisa R. Giniatullina, Sara Wojciechowski, Fatma Tore, Albert Rizvanov, Jari Koistinaho, Tarja Malm, Rashid Giniatullin
FRONTIERS IN CELLULAR NEUROSCIENCE
(2019)
Article
Neurosciences
Nikita Mikhailov, Jarkko Leskinen, Ilkka Fagerlund, Ekaterina Poguzhelskaya, Raisa Giniatullina, Oleg Gafurov, Tarja Malm, Tero Karjalainen, Olli Grohn, Rashid Giniatullin
Article
Clinical Neurology
Kasper Katisko, Eino Solje, Paula Korhonen, Olli Jaaskelainen, Sanna Loppi, Paivi Hartikainen, Anne M. Koivisto, Aleksi Kontkanen, Ville E. Korhonen, Seppo Helisalmi, Tarja Malm, Sanna-Kaisa Herukka, Anne M. Remes, Annakaisa Haapasalo
JOURNAL OF NEUROLOGY
(2020)
Article
Cell & Tissue Engineering
Henna Konttinen, Mauricio e Castro Cabral-da-Silva, Sohvi Ohtonen, Sara Wojciechowski, Anastasia Shakirzyanova, Simone Caligola, Rosalba Giugno, Yevheniia Ishchenko, Damian Hernandez, Mohammad Feroze Fazaludeen, Shaila Eamen, Mireia Gomez Budia, Ilkka Fagerlund, Flavia Scoyni, Paula Korhonen, Nadine Huber, Annakaisa Haapasalo, Alex W. Hewitt, James Vickers, Grady C. Smith, Minna Oksanen, Caroline Graff, Katja M. Kanninen, Sarka Lehtonen, Nicholas Propson, Michael P. Schwartz, Alice Pebay, Jari Koistinaho, Lezanne Ooi, Tarja Malm
Article
Medicine, General & Internal
Jere Paavola, Tarja Alakoski, Johanna Ulvila, Teemu Kilpio, Juuso Siren, Sanni Perttunen, Suneeta Narumanchi, Hong Wang, Ruizhu Lin, Katja Porvari, Juhani Junttila, Heikki Huikuri, Katariina Immonen, Paivi Lakkisto, Johanna Magga, Ilkka Tikkanen, Risto Kerkela
Article
Biochemistry & Molecular Biology
Zoltan Szabo, Laura Vainio, Ruizhu Lin, Julia Swan, Juha J. Hulmi, Lea Rahtu-Korpela, Raisa Scrpi, Mika Laitinen, Arja Pasternack, Olli Ritvos, Risto Kerkela, Johanna Magga
Article
Medicine, Research & Experimental
Ruizhu Lin, Lea Rahtu-Korpela, Johanna Magga, Johanna Ulvila, Julia Swan, Anna Kemppi, Lasse Pakanen, Katja Porvari, Heikki Huikuri, Juhani Junttila, Risto Kerkela
MOLECULAR THERAPY-NUCLEIC ACIDS
(2020)
Article
Biochemistry & Molecular Biology
Laura Vainio, Saija Taponen, Sini M. Kinnunen, Eveliina Halmetoja, Zoltan Szabo, Tarja Alakoski, Johanna Ulvila, Juhani Junttila, Paivi Lakkisto, Johanna Magga, Risto Kerkela
Summary: Phosphorylation of GSK3 beta at S389 enhances cardiomyocyte survival and protects from cardiomyocyte hypertrophy. The GSK3 beta S389A mutation promotes cardiomyocyte growth by activating the mTOR complex 1 signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Ruizhu Lin, Lea Rahtu-Korpela, Zoltan Szabo, Anna Kemppi, Sini Skarp, Antti M. Kiviniemi, E. Samuli Lepojarvi, Eveliina Halmetoja, Teemu Kilpio, Katja Porvari, Lasse Pakanen, Johanna Tolva, Riitta Paakkanen, Heli Segersvard, Ilkka Tikkanen, Mika Laine, Juha Sinisalo, Paivi Lakkisto, Heikki Huikuri, Johanna Magga, Juhani Junttila, Risto Kerkela
Summary: In this study, miR-185-5p was identified as a regulator of myocardial fibrosis by targeting the apelin receptor. This finding provides a potential therapeutic target for the treatment of cardiac fibrosis.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Tapio Roning, Johanna Magga, Anna Laitakari, Riikka Halmetoja, Joona Tapio, Elitsa Y. Dimova, Zoltan Szabo, Lea Rahtu-Korpela, Anna Kemppi, Gail Walkinshaw, Johanna Myllyharju, Risto Kerkela, Peppi Koivunen, Raisa Serpi
Summary: The study demonstrated that deficiency of Hif-p4h-2 gene leads to better preserved cardiac function and reduced cardiomyocyte hypertrophy during aging, possibly through upregulation of Notch signaling pathway and the target gene Hey2. Activation of the hypoxia response pathway could have therapeutic potential for combating age-induced cardiac hypertrophy.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Clinical Neurology
Irene F. Ugidos, Cristiana Piston, Paula Korhonen, Mireia Gomez-Buda, Valeriia Sitnikova, Pamela Klecki, Lveta Stanova, Jukka Jolkkonene, Tarja Malm
Summary: Stroke is a leading cause of death worldwide with limited therapeutic options currently available. Research has shown that sex differences play a significant role in stroke treatment and outcomes, with sexual hormones and aging being key factors influencing these differences.
Article
Biochemistry & Molecular Biology
Eveliina Halmetoja, Irina Nagy, Zoltan Szabo, Tarja Alakoski, Raisa Yrjola, Laura Vainio, Eliina Viitavaara, Ruizhu Lin, Lea Rahtu-Korpela, Seppo Vainio, Risto Kerkela, Johanna Magga
Summary: Wnt11 is involved in early cardiac development and left ventricular compaction, but its role in postnatal cardiac maturation and response to stress in the adult heart is not well understood. This study found that Wnt11 deficiency does not affect cardiomyocyte proliferation or maturation, but does lead to enlargement of the heart. Additionally, Wnt11 deficiency does not exacerbate cardiac hypertrophy or remodeling in response to pressure overload.
Article
Medicine, Research & Experimental
Ruizhu Lin, Juhani Junttila, Jarkko Piuhola, E. Samuli Lepojarvi, Johanna Magga, Antti M. Kiviniemi, Juha Perkiomaki, Heikki Huikuri, Olavi Ukkola, Mikko Tulppo, Risto Kerkela
Summary: Lin et al. found that increased levels of endothelin-1 are associated with higher mortality risk in patients with stable coronary artery disease. They also discovered that high intensity statin therapy can reduce the risk of death in patients with high endothelin-1 levels. These findings are important for the management of coronary artery disease patients.
COMMUNICATIONS MEDICINE
(2023)
Article
Neurosciences
Paula Korhonen, Eveliina Pollari, Katja M. Kanninen, Ekaterina Savchenko, Sarka Lehtonen, Sara Wojciechowski, Yuriy Pomeshchik, Ludo Van den Bosch, Gundars Goldsteins, Jari Koistinaho, Tarja Malm