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Author Masashi Kitazawa

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Assessing the activation/inhibition of tyrosine kinase-related pathways with a newly developed platform.

Harumi Kagiwada, Takayuki Kiboku, Hitomi Matsuo, Masashi Kitazawa, Kazuhiko Fukui, Katsuhisa Horimoto,

The phosphorylation of cellular proteins plays a crucial role in the transduction of various signals from outside the cell into the nucleus. The signals are transduced by phosphorylation chain reactions within multiple pathways; however, determining which pathways are responsible for each defined signal has proven challenging. To estimate the activity ... Read more >>

Proteomics (Proteomics)
[2021, 21(16):e2000251]

Cited: 0 times

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Effect of Lipopolysaccharide and TNFα on Neuronal Ascorbic Acid Uptake.

Veedamali S Subramanian, Trevor Teafatiller, Anshu Agrawal, Masashi Kitazawa, Jonathan S Marchant,

Vitamin C (ascorbic acid: AA) uptake in neurons occurs via the sodium-dependent vitamin C transporter-2 (SVCT2), which is highly expressed in the central nervous system (CNS). During chronic neuroinflammation or infection, CNS levels of lipopolysaccharide (LPS) and LPS-induced tumor necrosis factor-<i>α</i> (TNF<i>α</i>) are increased. Elevated levels of LPS and TNF<i>α</i> ... Read more >>

Mediators Inflamm (Mediators of inflammation)
[2021, 2021:4157132]

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Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology.

David Baglietto-Vargas, Stefania Forner, Lena Cai, Alessandra C Martini, Laura Trujillo-Estrada, Vivek Swarup, Marie Minh Thu Nguyen, Kelly Do Huynh, Dominic I Javonillo, Kristine Minh Tran, Jimmy Phan, Shan Jiang, Enikö A Kramár, Cristina Nuñez-Diaz, Gabriela Balderrama-Gutierrez, Franklin Garcia, Jessica Childs, Carlos J Rodriguez-Ortiz, Juan Antonio Garcia-Leon, Masashi Kitazawa, Mohammad Shahnawaz, Dina P Matheos, Xinyi Ma, Celia Da Cunha, Ken C Walls, Rahasson R Ager, Claudio Soto, Antonia Gutierrez, Ines Moreno-Gonzalez, Ali Mortazavi, Andrea J Tenner, Grant R MacGregor, Marcelo Wood, Kim N Green, Frank M LaFerla,

The majority of Alzheimer's disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. ... Read more >>

Nat Commun (Nature communications)
[2021, 12(1):2421]

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Inflammatory Cytokine IL-1β Downregulates Endothelial LRP1 via MicroRNA-mediated Gene Silencing.

Heng-Wei Hsu, Carlos J Rodriguez-Ortiz, Joannee Zumkehr, Masashi Kitazawa,

Effective clearance of neurotoxic amyloid-beta (Aβ) from the brain is a critical process to prevent Alzheimer's disease (AD). One major clearance mechanism is Aβ transcytosis mediated by low-density lipoprotein receptor-related protein 1 (LRP1) in capillary endothelial cells. A marked loss of endothelial LRP1 is found in AD brains and is ... Read more >>

Neuroscience (Neuroscience)
[2021, 453:69-80]

Cited: 0 times

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Chronic copper exposure directs microglia towards degenerative expression signatures in wild-type and J20 mouse model of Alzheimer's disease.

Siok Lam Lim, Carlos J Rodriguez-Ortiz, Heng-Wei Hsu, Jie Wu, Joannee Zumkehr, Jason Kilian, Janielle Vidal, Pinar Ayata, Masashi Kitazawa,

<h4>Background</h4>Copper (Cu) is an essential metal mediating a variety of vital biological reactions with its redox property. Its dyshomeostasis has been associated with accelerated cognitive decline and neurodegenerative disorders, such as Alzheimer's disease (AD). However, underlying neurotoxic mechanisms elicited by dysregulated Cu remain largely elusive. We and others previously demonstrated ... Read more >>

J Trace Elem Med Biol (Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS))
[2020, 62:126578]

Cited: 1 time

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Promotion of the Warburg effect is associated with poor benefit from adjuvant chemotherapy in colorectal cancer.

Masashi Kitazawa, Tomohisa Hatta, Yusuke Sasaki, Kazuhiko Fukui, Koji Ogawa, Eriko Fukuda, Naoki Goshima, Natsuko Okita, Yasuhide Yamada, Hitoshi Nakagama, Tohru Natsume, Katsuhisa Horimoto,

Metabolic reprogramming, including the Warburg effect, is a hallmark of cancer. Indeed, the diversity of cancer metabolism leads to cancer heterogeneity, but accurate assessment of metabolic properties in tumors has not yet been undertaken. Here, we performed absolute quantification of the expression levels of 113 proteins related to carbohydrate metabolism ... Read more >>

Cancer Sci (Cancer science)
[2020, 111(2):658-666]

Cited: 6 times

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Genetic Ablation of Hematopoietic Cell Kinase Accelerates Alzheimer's Disease-Like Neuropathology in Tg2576 Mice.

Siok Lam Lim, Diana Nguyen Tran, Zanett Kieu, Christine Chen, Emmanuel Villanueva, Sagar Ghiaar, Victoria Gallup, Joannee Zumkehr, David H Cribbs, Carlos J Rodriguez-Ortiz, Masashi Kitazawa,

Microglial dysregulation, pertaining to impairment in phagocytosis, clearance and containment of amyloid-β (Aβ), and activation of neuroinflammation, has been posited to contribute to the pathogenesis of Alzheimer's disease (AD). Detailed cellular mechanisms that are disrupted during the disease course to display such impairment in microglia, however, remain largely undetermined. We ... Read more >>

Mol Neurobiol (Molecular neurobiology)
[2020, 57(5):2447-2460]

Cited: 2 times

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Therapeutic Efficacy and Safety of Lenvatinib for Unresectable Hepatocellular Carcinoma Beyond Progression with Sorafenib

Tetsu Tomonari, Yasushi Sato, Hironori Tanaka, Takahiro Tanaka, Yasuteru Fujino, Yasuhiro Mitsui, Akihiro Hirao, Tatsuya Taniguchi, Koichi Okamoto, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Harumi Kagiwada, Masashi Kitazawa, Kazuhiko Fukui, Katsuhisa Horimoto, Tetsuji Takayama,

<h4>Background & Aims</h4> The efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line treatment of LEN, investigated the sensitivity of SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and their signal transduction pathway ... Read more >>

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CD4+ T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy.

Hiroshi Kagamu, Shigehisa Kitano, Ou Yamaguchi, Kenichi Yoshimura, Katsuhisa Horimoto, Masashi Kitazawa, Kazuhiko Fukui, Ayako Shiono, Atsuhito Mouri, Fuyumi Nishihara, Yu Miura, Kosuke Hashimoto, Yoshitake Murayama, Kyoichi Kaira, Kunihiko Kobayashi,

Accumulating evidence indicates that CD8<sup>+</sup> T cells in the tumor microenvironment and systemic CD4<sup>+</sup> T-cell immunity play an important role in mediating durable antitumor responses. We longitudinally examined T-cell immunity in the peripheral blood of patients with non-small lung cancer and found that responders had significantly (<i>P</i> < 0.0001) higher ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2020, 8(3):334-344]

Cited: 33 times

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Copper-Induced Upregulation of MicroRNAs Directs the Suppression of Endothelial LRP1 in Alzheimer's Disease Model.

Heng-Wei Hsu, Carlos J Rodriguez-Ortiz, Siok Lam Lim, Joannee Zumkehr, Jason G Kilian, Janielle Vidal, Masashi Kitazawa,

Chronic exposure to copper and its dyshomeostasis have been linked to accelerated cognitive decline and potentially increasing risk for Alzheimer's disease (AD). We and others have previously demonstrated that exposure to copper through drinking water significantly increased parenchymal amyloid-beta (Aβ) plaques and decreased endothelial low-density lipoprotein receptor-related protein 1 (LRP1) ... Read more >>

Toxicol Sci (Toxicological sciences : an official journal of the Society of Toxicology)
[2019, 170(1):144-156]

Cited: 4 times

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Metal Toxicity Links to Alzheimer's Disease and Neuroinflammation.

Tee Jong Huat, Judith Camats-Perna, Estella A Newcombe, Nicholas Valmas, Masashi Kitazawa, Rodrigo Medeiros,

As the median age of the population increases, the number of individuals with Alzheimer's disease (AD) and the associated socio-economic burden are predicted to worsen. While aging and inherent genetic predisposition play major roles in the onset of AD, lifestyle, physical fitness, medical condition, and social environment have emerged as ... Read more >>

J Mol Biol (Journal of molecular biology)
[2019, 431(9):1843-1868]

Cited: 38 times

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Impaired AMPA signaling and cytoskeletal alterations induce early synaptic dysfunction in a mouse model of Alzheimer's disease.

David Baglietto-Vargas, Gilberto Aleph Prieto, Agenor Limon, Stefania Forner, Carlos J Rodriguez-Ortiz, Kenji Ikemura, Rahasson R Ager, Rodrigo Medeiros, Laura Trujillo-Estrada, Alessandra C Martini, Masashi Kitazawa, Jose C Davila, Carl W Cotman, Antonia Gutierrez, Frank M LaFerla,

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that impairs memory and causes cognitive and psychiatric deficits. New evidences indicate that AD is conceptualized as a disease of synaptic failure, although the molecular and cellular mechanisms underlying these defects remain to be elucidated. Determining the timing and nature of the ... Read more >>

Aging Cell (Aging cell)
[2018, 17(4):e12791]

Cited: 20 times

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Inflammatory Cytokine, IL-1β, Regulates Glial Glutamate Transporter via microRNA-181a in vitro.

Joannee Zumkehr, Carlos J Rodriguez-Ortiz, Rodrigo Medeiros, Masashi Kitazawa,

Glutamate overload triggers synaptic and neuronal loss that potentially contributes to neurodegenerative diseases including Alzheimer's disease (AD). Glutamate clearance and regulation at synaptic clefts is primarily mediated by glial glutamate transporter 1 (GLT-1). We determined that inflammatory cytokines significantly upregulated GLT-1 through microRNA-181a-mediated post-transcriptional modifications. Unveiling the key underlying mechanisms ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2018, 63(3):965-975]

Cited: 3 times

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Determination of Rate-Limiting Factor for Formation of Beta-Catenin Destruction Complexes Using Absolute Protein Quantification.

Masashi Kitazawa, Tomohisa Hatta, Koji Ogawa, Eriko Fukuda, Naoki Goshima, Tohru Natsume,

Wnt/β-catenin signaling plays important roles in both ontogenesis and development. In the absence of a Wnt stimulus, β-catenin is degraded by a multiprotein "destruction complex" that includes Axin, APC, GSK3B, and FBXW11. Although the key molecules required for transducing Wnt signals have been identified, a quantitative understanding of this pathway ... Read more >>

J Proteome Res (Journal of proteome research)
[2017, 16(10):3576-3584]

Cited: 6 times

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Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model.

Tomoaki Nakazono, Travis N Lam, Ayushi Y Patel, Masashi Kitazawa, Takashi Saito, Takaomi C Saido, Kei M Igarashi,

The entorhinal cortex (EC) has bidirectional connections with the hippocampus and plays a critical role in memory formation and retrieval. EC is one of the most vulnerable regions in the brain in early stages of Alzheimer's disease (AD), a neurodegenerative disease with progressive memory impairments. Accumulating evidence from healthy behaving ... Read more >>

Front Syst Neurosci (Frontiers in systems neuroscience)
[2017, 11:48]

Cited: 19 times

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Astrocyte transport of glutamate and neuronal activity reciprocally modulate tau pathology in Drosophila.

Jason G Kilian, Heng-Wei Hsu, Kenneth Mata, Fred W Wolf, Masashi Kitazawa,

Abnormal buildup of the microtubule associated protein tau is a major pathological hallmark of Alzheimer's disease (AD) and various tauopathies. The mechanisms by which pathological tau accumulates and spreads throughout the brain remain largely unknown. Previously, we demonstrated that a restoration of the major astrocytic glutamate transporter, GLT1, ameliorated a ... Read more >>

Neuroscience (Neuroscience)
[2017, 348:191-200]

Cited: 5 times

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The Myoblast C2C12 Transfected with Mutant Valosin-Containing Protein Exhibits Delayed Stress Granule Resolution on Oxidative Stress.

Carlos J Rodriguez-Ortiz, Julio C Flores, Joanna A Valenzuela, Gema J Rodriguez, Joannee Zumkehr, Diana N Tran, Virginia E Kimonis, Masashi Kitazawa,

Valosin-containing protein (VCP) mutations cause inclusion body myopathy with Paget disease and frontotemporal dementia. However, the mechanisms by which mutant VCP triggers degeneration remain unknown. Here, we investigated the role of VCP in cellular stress and found that the oxidative stressor arsenite and heat shock-activated stress responses evident by T-intracellular ... Read more >>

Am J Pathol (The American journal of pathology)
[2016, 186(6):1623-1634]

Cited: 3 times

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Infection, systemic inflammation, and Alzheimer's disease.

Siok Lam Lim, Carlos J Rodriguez-Ortiz, Masashi Kitazawa,

Alzheimer's disease (AD) is a leading cause of dementia among elderly. Yet, its etiology remains largely unclear. In this review, we summarize studies that associate systemic infection and neuroinflammation with AD, while highlighting that early-life or life-long exposure to infectious agents predisposes one to develop AD at a later age. ... Read more >>

Microbes Infect (Microbes and infection)
[2015, 17(8):549-556]

Cited: 43 times

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Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer's disease.

Joannee Zumkehr, Carlos J Rodriguez-Ortiz, David Cheng, Zanett Kieu, Thin Wai, Charlesice Hawkins, Jason Kilian, Siok Lam Lim, Rodrigo Medeiros, Masashi Kitazawa,

Glial glutamate transporter, GLT-1, is the major Na(+)-driven glutamate transporter to control glutamate levels in synapses and prevent glutamate-induced excitotoxicity implicated in neurodegenerative disorders including Alzheimer's disease (AD). Significant functional loss of GLT-1 has been reported to correlate well with synaptic degeneration and severity of cognitive impairment among AD patients, ... Read more >>

Neurobiol Aging (Neurobiology of aging)
[2015, 36(7):2260-2271]

Cited: 52 times

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Restoration of lipoxin A4 signaling reduces Alzheimer's disease-like pathology in the 3xTg-AD mouse model.

Haley C Dunn, Rahasson R Ager, David Baglietto-Vargas, David Cheng, Masashi Kitazawa, David H Cribbs, Rodrigo Medeiros,

The initiation of an inflammatory response is critical to the survival of an organism. However, when inflammation fails to reach resolution, a chronic inflammatory state may occur, potentially leading to bystander tissue damage. Accumulating evidence suggests that chronic inflammation contributes to the progression of Alzheimer's disease (AD), and identifying mechanisms ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2015, 43(3):893-903]

Cited: 31 times

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Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain.

Monica R P Elmore, Allison R Najafi, Maya A Koike, Nabil N Dagher, Elizabeth E Spangenberg, Rachel A Rice, Masashi Kitazawa, Bernice Matusow, Hoa Nguyen, Brian L West, Kim N Green,

The colony-stimulating factor 1 receptor (CSF1R) is a key regulator of myeloid lineage cells. Genetic loss of the CSF1R blocks the normal population of resident microglia in the brain that originates from the yolk sac during early development. However, the role of CSF1R signaling in microglial homeostasis in the adult ... Read more >>

Neuron (Neuron)
[2014, 82(2):380-397]

Cited: 598 times

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Upregulation of miR-181 decreases c-Fos and SIRT-1 in the hippocampus of 3xTg-AD mice.

Carlos J Rodriguez-Ortiz, David Baglietto-Vargas, Hilda Martinez-Coria, Frank M LaFerla, Masashi Kitazawa,

MicroRNAs are a group of small RNAs that regulate diverse cellular processes including neuronal function. Recent studies have shown that dysregulation of specific microRNAs is critically involved in the development of Alzheimer's disease (AD). Most of these reports have focused on microRNAs implicated in alterations of amyloid-β and tau. However, ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2014, 42(4):1229-1238]

Cited: 34 times

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α7 Nicotinic receptor agonist enhances cognition in aged 3xTg-AD mice with robust plaques and tangles.

Rodrigo Medeiros, Nicholas A Castello, David Cheng, Masashi Kitazawa, David Baglietto-Vargas, Kim N Green, Timothy A Esbenshade, Robert S Bitner, Michael W Decker, Frank M LaFerla,

Alzheimer disease (AD) is a progressive neurodegenerative disorder with associated memory loss, spatial disorientation, and other psychiatric problems. Cholinergic system dysfunction is an early and salient feature of AD, and enhancing cholinergic signaling with acetylcholinesterase inhibitors is currently the primary strategy for improving cognition. The beneficial effects of acetylcholinesterase inhibitors, ... Read more >>

Am J Pathol (The American journal of pathology)
[2014, 184(2):520-529]

Cited: 35 times

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Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition.

David Baglietto-Vargas, Masashi Kitazawa, Elaine J Le, Tatiana Estrada-Hernandez, Carlos J Rodriguez-Ortiz, Rodrigo Medeiros, Kim N Green, Frank M LaFerla,

Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we developed a novel transgenic ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2014, 62:407-415]

Cited: 12 times

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Aspirin-triggered lipoxin A4 stimulates alternative activation of microglia and reduces Alzheimer disease-like pathology in mice.

Rodrigo Medeiros, Masashi Kitazawa, Giselle F Passos, David Baglietto-Vargas, David Cheng, David H Cribbs, Frank M LaFerla,

Microglia play an essential role in innate immunity, homeostasis, and neurotropic support in the central nervous system. In Alzheimer disease (AD), these cells may affect disease progression by modulating the buildup of β-amyloid (Aβ) or releasing proinflammatory cytokines and neurotoxic substances. Discovering agents capable of increasing Aβ uptake by phagocytic ... Read more >>

Am J Pathol (The American journal of pathology)
[2013, 182(5):1780-1789]

Cited: 69 times

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