Article
Biochemistry & Molecular Biology
Marta Sidoryk-Wegrzynowicz, Beata Dabrowska-Bouta, Grzegorz Sulkowski, Lidia Struzynska
Summary: Tau-dependent neurodegeneration in a transgenic mouse model is accompanied by astrocytosis, indicating the critical role of astrocytes in the disease development. Alterations in glutamine transport and recycling affect the neuronal-astrocytic integrity, suggesting potential mechanisms operating in Tau pathology.
NEUROCHEMISTRY INTERNATIONAL
(2023)
Editorial Material
Biology
George Andrew S. Inglis
Summary: The study shows that conditional deletion of the alpha 2-Na/K ATPase in astrocytes can lead to episodic paralysis in mice, potentially due to altered metabolism of serine and glycine.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Zhuchen Zhou, Jing Zhou, Jie Liao, Zhong Chen, Yanrong Zheng
Summary: Astrocytes contribute to maintaining cerebral homeostasis and have a significant role in various disorders through autophagy.
NEUROCHEMICAL RESEARCH
(2022)
Article
Neurosciences
Olga Tyurikova, Pei-Yu Shih, Yulia Dembitskaya, Leonid P. Savtchenko, Thomas J. McHugh, Dmitri A. Rusakov, Alexey Semyanov
Summary: Glutamatergic transmission through postsynaptic NMDA receptors induces K+ efflux, which enhances glutamate release in astrocytes and reduces glutamate uptake, forming a feedback loop.
Article
Biochemistry & Molecular Biology
Xue-Chun Ni, Hong-Fei Wang, Yuan-Yuan Cai, Dai Yang, Raphael N. Alolga, Baolin Liu, Jia Li, Feng-Qing Huang
Summary: This study found that ginsenoside Rb1 could protect neurons from ischemic injury by inhibiting astrocyte activation, protecting mitochondria, and promoting mitochondrial transfer from astrocytes to neurons.
Article
Neurosciences
Keyong Li, Elizabeth C. Gonye, Ruth L. Stornetta, Christopher B. Bayliss, Grace Yi, Daniel S. Stornetta, Serapio M. Baca, Stephen B. G. Abbott, Patrice G. Guyenet, Douglas A. Bayliss
Summary: The role of astrocytic Na+-HCO3- cotransporter NBCe1 in the respiratory response to chemoreceptor stimuli was investigated in mice. Conditional knockout of Slc4a4 in astrocytes did not affect the CO2-induced activation of neurons or astrocytes, CO2-stimulated breathing, or hypoxia-stimulated breathing. These results suggest that astrocytic NBCe1 is not required for the respiratory responses in mice and that other NBCe1-independent mechanisms are involved.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Review
Neurosciences
Marta Sobolczyk, Tomasz Boczek
Summary: Astrocytes play a crucial role in neurotransmission by interacting with synapses and modulating cAMP-PKA pathway to regulate neurotransmitter synthesis and release for neuroprotection. Alterations at the Ca2+/cAMP crosstalk have been identified in neurodegenerative disorders.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Rajkumar Rajanathan, Tina Myhre Pedersen, Halvor Osterby Guldbrandsen, Lenette Foldager Olesen, Morten B. Thomsen, Hans Erik Botker, Vladimir V. Matchkov
Summary: Heterozygous mice for the migraine-associated mutation (G301R) in the Na+,K+-ATPase alpha(2)-isoform have decreased expression of cardiovascular alpha(2)-isoform and exhibit a pro-contractile vascular phenotype associated with reduced cardiac efficiency. This study aims to assess the functional contribution of the alpha(2)-isoform to in vivo cardiovascular function and showed that the ouabain-induced vascular response was augmented in alpha(+/G301R)(2) mice, leading to suppressed cardiac function.
Article
Biochemistry & Molecular Biology
Jureepon Roboon, Tsuyoshi Hattori, Hiroshi Ishii, Mika Takarada-Iemata, Dinh Thi Nguyen, Collin D. Heer, Denis O'Meally, Charles Brenner, Yasuhiko Yamamoto, Hiroshi Okamoto, Haruhiro Higashida, Osamu Hori
Summary: Neuroinflammation is a critical pathological process in various neurological conditions, and the direct impact of brain NAD(+) levels and CD38 gene on neuroinflammation has been demonstrated. Inhibiting CD38 and supplementing NAD(+) can effectively suppress neuroinflammation.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Clinical Neurology
Yang Liao, Yingyi Wang, Qing-Qing Tao, Chaoguang Yang, Jinlei Wang, Jinbo Cheng, Jun Ma, Zhi-Ying Wu, Rui-Yuan Pan, Zengqiang Yuan
Summary: This study found a significant association between CALHM2 V136G mutation and AD, which resulted in the loss of CALHM2 function and impaired synaptic plasticity. Mice with the mutation displayed depressive-like behaviors and cognitive decline in old age. These findings suggest that CALHM2 dysfunction may contribute to the clinical correlation between depression and AD.
ALZHEIMERS & DEMENTIA
(2023)
Article
Cell Biology
Suchan Liao, Ying Luo, Titikorn Chunchai, Kodchanan Singhanat, Busarin Arunsak, Juthipong Benjanuwattra, Nattayaporn Apaijai, Nipon Chattipakorn, Siriporn C. Chattipakorn
Summary: This study reveals that cardiac dysfunction, brain apoptosis, brain inflammation, microglial hyperactivation, and reactive astrogliosis occur following myocardial infarction and ischemia-reperfusion injury. Pretreatment with Z-VAD can attenuate brain apoptosis, reduce brain inflammation, suppress microglial and astrocytic hyperactivation and proliferation, and improve cardiac function, suggesting its neuroprotective effects against cardiac I/R injury.
INFLAMMATION RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Alisa A. Markina, Rogneda B. Kazanskaya, Julia A. Timoshina, Vladislav A. Zavialov, Denis A. Abaimov, Anna B. Volnova, Tatiana N. Fedorova, Raul R. Gainetdinov, Alexander V. Lopachev
Summary: In recent years, it has been discovered that cardiotonic steroids, which are Na+,K+-ATPase ligands, play important roles in the physiological and pathophysiological processes in the body. However, their functions in the central nervous system are not well understood. This review aims to discuss the involvement of cardiotonic steroids and Na+,K+-ATPase in dopaminergic system pathologies, as well as their potential roles in neurodegenerative diseases.
Article
Critical Care Medicine
Daniel C. Lu, Zsolt Zador, Jinghua Yao, Farbod Fazlollahi, Geoffrey T. Manley
Summary: This study demonstrates a protective role of AQP4 in post-traumatic seizure susceptibility by promoting astrogliosis, formation of a glial scar, and preventing microgliosis.
JOURNAL OF NEUROTRAUMA
(2021)
Article
Biochemistry & Molecular Biology
Violetta V. Kravtsova, Arina A. Fedorova, Maria Tishkova, Alexandra A. Livanova, Oleg V. Vetrovoy, Alexander G. Markov, Vladimir V. Matchkov, Igor I. Krivoi
Summary: This study investigated the protective effect of ouabain on ionizing radiation-induced disturbances in skeletal muscle Na,K-ATPase function. Ouabain was found to prevent depolarization and loss of electrogenic contribution of the alpha 2 isozyme of Na,K-ATPase, accompanied by an increase in circulating ouabain concentration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Integrative & Complementary Medicine
Li-tian Ma, Yang Bai, Jie Li, Yu Qiao, Yang Liu, Jin Zheng
Summary: Elemene alleviated mechanical allodynia and anxiety in rats with SNI possibly by downregulating the expression of NDRG2 in spinal astrocytes.
CHINESE JOURNAL OF INTEGRATIVE MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Yin Xu, Shuqi Du, Jacob A. Marsh, Kanta Horie, Chihiro Sato, Andrea Ballabio, Celeste M. Karch, David M. Holtzman, Hui Zheng
Summary: The transcription factor EB (TFEB) plays a crucial role in the lysosomal exocytosis of selected tau species, with TFEB loss causing a decrease in tau levels and accelerated spreading within neurons. This suggests that TFEB-mediated tau exocytosis acts as a clearance mechanism to reduce intracellular tau levels under pathological conditions.
MOLECULAR PSYCHIATRY
(2021)
Article
Geriatrics & Gerontology
Lauren N. Koenig, Pamela LaMontagne, Matthew F. Glasser, Randall Bateman, David Holtzman, Igor Yakushev, Jasmeer Chhatwal, Gregory S. Day, Clifford Jack, Catherine Mummery, Richard J. Perrin, Brian A. Gordon, John C. Morris, Joshua S. Shimony, Tammie L. S. Benzinger
Summary: Brain atrophy is common in aging, especially in temporal lobe and subcortical regions. The rate of atrophy varies in different brain regions, being linear in temporal lobe, faster in subcortical regions at later ages, and slower in frontal regions at later ages. This age-derivative pattern is associated with myelin levels.
NEUROBIOLOGY OF AGING
(2022)
Article
Medicine, Research & Experimental
Lubov A. Ezerskiy, Kathleen M. Schoch, Chihiro Sato, Mariana Beltcheva, Kanta Horie, Frank Rigo, Ryan Martynowicz, Celeste M. Karch, Randall J. Bateman, Timothy M. Miller
Summary: This study finds that abnormal expression of 4R tau in astrocytes is associated with the progression of neurodegenerative diseases. Increasing the expression of 4R tau in astrocytes leads to increased expression of neurotoxic genes and dysregulation of homeostatic function. In addition, co-culturing healthy neurons with astrocytes expressing 4R tau results in abnormal firing frequency and hypersynchrony of neurons.
Review
Immunology
Samira Parhizkar, David M. Holtzman
Summary: Neuroinflammation is a key mechanism in neurodegenerative diseases such as Alzheimer's disease (AD), and APOE4 directly influences disease onset and progression by interacting with AD's pathological features. Microglia and astrocytes, the immune cells in the brain, play important roles in promoting neuronal health, but under disease conditions, they become dysfunctional and contribute to chronic inflammation-induced neurodegeneration.
SEMINARS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rashmi Yadav, Shamulailatpam Shreedarshanee Devi, Jyoti Oswalia, Sivaprakash Ramalingam, Ranjana Arya
Summary: Limited treatment options and research in understanding rare diseases like GNE Myopathy has raised concerns about therapeutic development. The study focuses on the mechanism of protein aggregate formation in GNE mutant cells, revealing HSP70 as a promising therapeutic target in reducing protein aggregation through activators like BGP-15.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Immunology
Nimansha Jain, Caroline A. Lewis, Jason D. Ulrich, David M. Holtzman
Summary: Variants in the TREM2 gene are associated with increased risk for late-onset AD, and decreased function of TREM2 can affect microglial response to Aβ plaques. Chronic increase of TREM2 signaling may exacerbate the Aβ-induced tau pathology.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Review
Immunology
Xiaoying Chen, David M. Holtzman
Summary: Alzheimer's disease is the most common neurodegenerative disease with innate immune pathway regulators as genetic risk factors. Innate and adaptive immune responses play important roles in disease development and may serve as therapeutic targets.
Article
Biochemistry & Molecular Biology
Kanta Horie, Nicolas R. Barthelemy, Salvatore Spina, Lawren VandeVrede, Yingxin He, Ross W. Paterson, Brenton A. Wright, Gregory S. Day, Albert A. Davis, Celeste M. Karch, William W. Seeley, Richard J. Perrin, Rama K. Koppisetti, Faris Shaikh, Argentina Lario Lago, Hilary W. Heuer, Nupur Ghoshal, Audrey Gabelle, Bruce L. Miller, Adam L. Boxer, Randall J. Bateman, Chihiro Sato
Summary: Currently, there are no fluid biomarkers or imaging tracers available for the diagnosis and treatment of other tauopathies. This study identifies specific tau species that increase in the brains of patients with CBD, PSP, FTLD-MAPT, and AD, but decrease in their cerebrospinal fluid. Measurements of these specific tau species in cerebrospinal fluid can differentiate between different diseases and aid in the diagnosis and clinical trial design of primary tauopathies.
Article
Psychiatry
Sidhartha Mahali, Rita Martinez, Melvin King, Anthony Verbeck, Oscar Harari, Bruno A. Benitez, Kanta Horie, Chihiro Sato, Sally Temple, Celeste M. Karch
Summary: Disruption of lysosomal biogenesis and autophagic function is observed in FTLD-tau patients carrying a MAPT p.R406W mutation. Correction of the mutant allele reverses the morphological and functional deficits, and treatment with mTOR inhibitors leads to specific degradation of tau protein in MAPT p.R406W neurons.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Biochemical Research Methods
Elke Gabriel, Walid Albanna, Giovanni Pasquini, Anand Ramani, Natasa Josipovic, Aruljothi Mariappan, Maria Giovanna Riparbelli, Giuliano Callaini, Celeste M. M. Karch, Olivier Goureau, Argyris Papantonis, Volker Busskamp, Toni Schneider, Jay Gopalakrishnan
Summary: Induced pluripotent stem cell-derived brain organoids, known as OVB organoids, can deconstruct the developmental complexities of the human brain and help study interorgan interactions between optic vesicles and the brain. This protocol enables the generation of functional integrated bilateral optic vesicles and can be used to model early eye patterning defects.
Review
Biochemistry & Molecular Biology
Wade K. Self, David M. Holtzman
Summary: Alzheimer disease (AD) is the leading cause of dementia worldwide, and until recently, effective strategies to slow or prevent its clinical progression have been elusive. This review examines the latest advancements in biomarker technologies and therapeutic development for improving AD diagnosis and treatment. It discusses the use of neuroimaging and fluid-based biomarkers to stage AD pathology, focusing on the role of amyloid, tau, and neuroinflammation in disease progression. The review also highlights potential disease-modifying treatment targets and their implications for AD clinical care.