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TSPO alzheimer

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https://www.readbyqxmd.com/read/29925037/tspo-ligand-pk11195-improves-alzheimer-related-outcomes-in-aged-female-3xtg-ad-mice
#1
Amy Christensen, Christian J Pike
Alzheimer's disease (AD) pathogenesis is a multifactorial process that involves numerous pathways within the central nervous system. Thus, interventions that interact with several disease-related pathways may offer an increased opportunity for successful prevention and treatment of AD. Translocator protein 18 kD (TSPO) is a mitochondrial protein that is associated with regulation of many cellular processes including inflammation, steroid synthesis, apoptosis, and mitochondrial respiration. Although TSPO ligands have been shown to be protective in several neurodegenerative paradigms, little work has been done to assess their potential as treatments for AD...
June 17, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29608645/distinct-dynamic-profiles-of-microglial-activation-are-associated-with-progression-of-alzheimer-s-disease
#2
Lorraine Hamelin, Julien Lagarde, Guillaume Dorothée, Marie Claude Potier, Fabian Corlier, Bertrand Kuhnast, Fabien Caillé, Bruno Dubois, Ludovic Fillon, Marie Chupin, Michel Bottlaender, Marie Sarazin
Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheimer's disease, its actual impact on disease progression remains controversial, being reported as either detrimental or protective. This work aimed at investigating the temporal relationship between microglial activation and clinical progression of Alzheimer's disease. First, in a large cohort of patients with Alzheimer's disease we analysed the predictive value of microglial activation assessed by 18F-DPA-714 PET imaging on functional, cognitive and MRI biomarkers outcomes after a 2-year follow-up...
June 1, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29512083/imaging-of-microglial-activation-in-alzheimer-s-disease-by-11-c-pbr28-pet
#3
Cornelius K Donat, Nazanin Mirzaei, Sac-Pham Tang, Paul Edison, Magdalena Sastre
Deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD) are believed to be linked to microglial activation. A hallmark of reactive microglia is the upregulation of mitochondrial translocator protein (TSPO) expression. Positron emission tomography (PET) is a nuclear imaging technique that measures the distribution of trace doses of radiolabeled compounds in the body over time. PET imaging using the 2nd generation TSPO tracer [11 C]PBR28 provides an opportunity for accurate visualization and quantification of changes in microglial density in transgenic mouse models of Alzheimer's disease (AD)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29413519/imaging-translocator-protein-as-a-biomarker-of-neuroinflammation-in-dementia
#4
William C Kreisl, Ioline D Henter, Robert B Innis
Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET)...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29315754/tspo-regulation-in-reactive-gliotic-diseases
#5
REVIEW
Adam M McNeela, Charles Bernick, Rochelle M Hines, Dustin J Hines
The brain is the most metabolically active organ in the body. This high metabolic demand is apparent in that 60% of the brain is comprised of mitochondria-enriched cells. A disruption of the brain's ability to meet this immense metabolic demand is central to the pathogenesis of a multitude of neurological disorders, which range from depression to Alzheimer's disease. Central to these pathologies are glial signaling and energy metabolism cascades regulating apoptosis and inflammation. Thus, diseases causing inflammation and disruption of metabolism can be correlated with glial reactivity...
June 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29242722/recent-progress-in-the-development-of-tspo-pet-ligands-for-neuroinflammation-imaging-in-neurological-diseases
#6
REVIEW
Md Maqusood Alam, Jihye Lee, Sang-Yoon Lee
Neuroinflammation is heavily associated with various neurological diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and stroke. It is strongly characterized by the activation of microglia which can be visualized using position emission tomography (PET). Traditionally, translocator protein 18 kDa (TSPO) has been the preferred target for imaging the inflammatory progression of the microglial component. TSPO is expressed in the outer mitochondrial membrane and present in very low concentrations in the healthy human brain, but is markedly upregulated in response to brain injury and inflammation...
December 2017: Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29203457/non-invasive-estimation-of-11-c-pbr28-binding-potential
#7
Martin Schain, Francesca Zanderigo, R Todd Ogden, William C Kreisl
[11 C]PBR28 is a PET radioligand used to estimate densities of the 18 kDa translocator protein (TSPO) in vivo. Since there is no suitable reference region, arterial blood samples are required for full quantification. Here, we evaluate a methodology for full quantification of [11 C]PBR28 PET data that does not require either a reference region or blood samples. Simultaneous estimation (SIME) uses time-activity curves from several brain regions to estimate binding potential (BPND ), a theoretically more sensitive outcome measure than total distribution volume...
April 1, 2018: NeuroImage
https://www.readbyqxmd.com/read/29135331/imaging-microglial-activation-and-amyloid-burden-in-amnestic-mild-cognitive-impairment
#8
Dunja Knezevic, Nicolaas Paul Lg Verhoeff, Sina Hafizi, Antonio P Strafella, Ariel Graff-Guerrero, Tarek Rajji, Bruce G Pollock, Sylvain Houle, Pablo M Rusjan, Romina Mizrahi
Amnestic mild cognitive impairment (aMCI) is defined as a transitional state between normal aging and Alzheimer's disease (AD). Given the replicated finding of increased microglial activation in AD, we sought to investigate whether microglial activation is also elevated in aMCI and whether it is related to amyloid beta (Aβ) burden in-vivo . Eleven aMCI participants and 14 healthy volunteers completed positron emission tomography (PET) scans with [(18)F]-FEPPA and [(11)C]-PIB. Given the known sensitivity in affinity of second-generation TSPO radioligands, participants were genotyped for the TSPO polymorphism and only high-affinity binders were included...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29031071/discovery-of-thienopyrrolotriazine-derivatives-to-protect-mitochondrial-function-against-a%C3%AE-induced-neurotoxicity
#9
TaeHun Kim, Woo Seung Son, Mohammad Neaz Morshed, Ashwini M Londhe, Seo Yun Jung, Jong-Hyun Park, Woo-Kyu Park, Sang Min Lim, Ki Duk Park, Sung Jin Cho, Kyu-Sung Jeong, Jiyoun Lee, Ae Nim Pae
Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine group...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28988133/coupling-between-physiological-tspo-expression-in-brain-and-myocardium-allows-stabilization-of-late-phase-cerebral-18-f-ge180-pet-quantification
#10
Maximilian Deussing, Tanja Blume, Lena Vomacka, Christoph Mahler, Carola Focke, Andrei Todica, Marcus Unterrainer, Nathalie L Albert, Simon Lindner, Barbara von Ungern-Sternberg, Karlheinz Baumann, Andreas Zwergal, Peter Bartenstein, Jochen Herms, Axel Rominger, Matthias Brendel
OBJECTIVES: PET imaging of the 18 kDa translocator protein (TSPO), a biomarker of microglial activity, receives growing interest in clinical and preclinical applications of neuroinflammatory and neurodegenerative brain diseases. In globally affected brains, intra-cerebral pseudo reference regions are not feasible. Consequently, many brain-independent approaches have been attempted, including SUV analysis and normalization to muscle- or heart uptake, aiming to stabilize quantitative analysis...
January 15, 2018: NeuroImage
https://www.readbyqxmd.com/read/28986511/neuroinflammation-appears-early-on-pet-imaging-and-then-plateaus-in-a-mouse-model-of-alzheimer-disease
#11
Francisco R López-Picón, Anniina Snellman, Olli Eskola, Semi Helin, Olof Solin, Merja Haaparanta-Solin, Juha O Rinne
Neuroinflammation has been associated with various neurologic diseases, including Alzheimer disease (AD). In AD, the translocator protein 18 kDa (TSPO) is overexpressed in the activated microglia that surround the β-amyloid plaques. In the current longitudinal study using a mouse model of AD, we evaluated the association between β-amyloid deposition and neuroinflammation in AD. Methods: To monitor the longitudinal changes in β-amyloid deposition and neuroinflammation, we used in vivo PET imaging and ex vivo autoradiography with Pittsburgh compound B (11 C-PIB) and a TSPO tracer, flutriciclamide (18 F-GE-180), in the APP23 mouse model of AD...
March 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28901441/profiling-of-differentially-expressed-genes-in-adipose-tissues-of-multiple-symmetric-lipomatosis
#12
Ke Chen, Linghao Wang, Wenjun Yang, Changfa Wang, Gui Hu, Zhaohui Mo
Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by aberrant multiple and symmetric subcutaneous adipose tissue accumulation in the face, neck, shoulders, back, chest and abdomen, severely affecting the quality of life of patients. At present, precise MSL etiology and pathogenesis remain to be elucidated. The present study first utilized a digital gene expression technique with a next‑generation sequencing platform to profile differentially expressed genes in three cases of MSL vs. normal control tissue...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28559417/the-ftd-like-syndrome-causing-trem2-t66m-mutation-impairs-microglia-function-brain-perfusion-and-glucose-metabolism
#13
Gernot Kleinberger, Matthias Brendel, Eva Mracsko, Benedikt Wefers, Linda Groeneweg, Xianyuan Xiang, Carola Focke, Maximilian Deußing, Marc Suárez-Calvet, Fargol Mazaheri, Samira Parhizkar, Nadine Pettkus, Wolfgang Wurst, Regina Feederle, Peter Bartenstein, Thomas Mueggler, Thomas Arzberger, Irene Knuesel, Axel Rominger, Christian Haass
Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD). Homozygous TREM2 missense mutations, such as p.T66M, lead to the FTD-like syndrome, but how they cause pathology is unknown. Using CRISPR/Cas9 genome editing, we generated a knock-in mouse model for the disease-associated Trem2 p.T66M mutation. Consistent with a loss-of-function mutation, we observe an intracellular accumulation of immature mutant Trem2 and reduced generation of soluble Trem2 similar to patients with the homozygous p...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28545084/feasibility-study-of-tspo-quantification-with-18f-feppa-using-population-based-input-function
#14
Rostom Mabrouk, Antonio P Strafella, Dunja Knezevic, Christine Ghadery, Romina Mizrahi, Avideh Gharehgazlou, Yuko Koshimori, Sylvain Houle, Pablo Rusjan
PURPOSE: The input function (IF) is a core element in the quantification of Translocator protein 18 kDa with positron emission tomography (PET), as no suitable reference region with negligible binding has been identified. Arterial blood sampling is indeed needed to create the IF (ASIF). In the present manuscript we study individualization of a population based input function (PBIF) with a single arterial manual sample to estimate total distribution volume (VT) for [18F]FEPPA and to replicate previously published clinical studies in which the ASIF was used...
2017: PloS One
https://www.readbyqxmd.com/read/28533150/molecular-imaging-of-neuroinflammation-in-alzheimer-s-disease-and-mild-cognitive-impairment
#15
REVIEW
Dunja Knezevic, Romina Mizrahi
Neuroinflammatory changes have been demonstrated to be an important feature of Alzheimer's disease (AD); however, the exact role of neuroinflammation and its progression during disease is still not well understood. One of the main drivers of the neuroinflammatory process are microglial cells. Positron Emission Tomography allows for the quantification of microglial activation by labelling the Translocator Protein 18kDa (TSPO), which becomes overexpressed upon activation of microglial cells. Several radioligands have been designed to target TSPO and have been studied in-vivo in AD populations...
January 3, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28530834/a-facile-radiolabeling-of-18f-fdpa-via-spirocyclic-iodonium-ylides-preliminary-pet-imaging-studies-in-preclinical-models-of-neuroinflammation
#16
Lu Wang, Ran Cheng, Masayuki Fujinaga, Jian Yang, Yiding Zhang, Akiko Hatori, Katsushi Kumata, Jing Yang, Neil Vasdev, Yunfei Du, Chongzhao Ran, Ming-Rong Zhang, Steven H Liang
A suitable TSPO PET ligand may visualize and quantify neuroinflammation in a living brain. Herein we report a 18F-ligand, [18F]2 ([18F]FDPA), is radiolabeled in high yield and high specific activity based on our spirocyclic iodonium ylide (SCIDY) strategy. [18F]2 demonstrated saturable specific binding to TSPO, substantially elevated brain uptake, and slow washout of bound PET signal in the preclinical models of brain neuroinflammation (cerebral ischemia and Alzheimer's disease).
June 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28529627/-18-f-ge-180-pet-detects-reduced-microglia-activation-after-lm11a-31-therapy-in-a-mouse-model-of-alzheimer-s-disease
#17
Michelle L James, Nadia P Belichenko, Adam J Shuhendler, Aileen Hoehne, Lauren E Andrews, Christina Condon, Thuy-Vi V Nguyen, Vladimer Reiser, Paul Jones, William Trigg, Jianghong Rao, Sanjiv S Gambhir, Frank M Longo
Microglial activation is a key pathological feature of Alzheimer's disease (AD). PET imaging of translocator protein 18 kDa (TSPO) is a strategy to detect microglial activation in vivo . Here we assessed flutriciclamide ([18 F]GE-180), a new second-generation TSPO-PET radiotracer, for its ability to monitor response to LM11A-31, a novel AD therapeutic in clinical trials. AD mice displaying pathology were treated orally with LM11A-31 for 3 months. Subsequent [18 F]GE-180-PET imaging revealed significantly lower signal in cortex and hippocampus of LM11A-31-treated AD mice compared to those treated with vehicle, corresponding with decreased levels of TSPO immunostaining and microglial Iba1 immunostaining...
2017: Theranostics
https://www.readbyqxmd.com/read/28516240/in-vivo-pet-imaging-of-neuroinflammation-in-alzheimer-s-disease
#18
REVIEW
Julien Lagarde, Marie Sarazin, Michel Bottlaender
Increasing evidence suggests that neuroinflammation contributes to the pathophysiology of many neurodegenerative diseases, especially Alzheimer's disease (AD). Molecular imaging by PET may be a useful tool to assess neuroinflammation in vivo, thus helping to decipher the complex role of inflammatory processes in the pathophysiology of neurodegenerative diseases and providing a potential means of monitoring the effect of new therapeutic approaches. For this objective, the main target of PET studies is the 18 kDa translocator protein (TSPO), as it is overexpressed by activated microglia...
May 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28219319/withdrawn-biomarkers-in-alzheimer-s-disease-recent-update
#19
(no author information available yet)
Article Withdrawn
February 20, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/27855359/discovery-of-benzimidazole-derivatives-as-modulators-of-mitochondrial-function-a-potential-treatment-for-alzheimer-s-disease
#20
TaeHun Kim, Ha Yun Yang, Beoung Gun Park, Seo Yun Jung, Jong-Hyun Park, Ki Duk Park, Sun-Joon Min, Jinsung Tae, Hyejin Yang, Suengmok Cho, Sung Jin Cho, Hyundong Song, Inhee Mook-Jung, Jiyoun Lee, Ae Nim Pae
In this study, we designed a library of compounds based on the structures of well-known ligands of the 18 kDa translocator protein (TSPO), one of the putative components of the mPTP. We performed diverse mitochondrial functional assays to assess their ability to restore cells from Aβ-induced toxicity in vitro and in vivo. Among tested compounds, compound 25 effectively improved cognitive function in animal models of AD. Given the excellent in vitro and in vivo activity and a favorable pharmacokinetic profile of compound 25, we believe that it can serve as a promising lead compound for a potential treatment option for AD...
January 5, 2017: European Journal of Medicinal Chemistry
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