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1. The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors

Author

Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, AA, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Davies, JA, Abbracchio, MP, Abraham, G, Agoulnik, A, Alexander, W, Al-hosaini, K, Back, M, Baker, JG, Barnes, NM, Bathgate, R, Beaulieu, J-M, Beck-Sickinger, AG, Behrens, M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Brauner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, KJ, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Cox, HM, Csaba, Z, Dahlgren, C, Dent, G, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, Garelja, ML, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gratz, L, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Herr, D, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, Ijzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Larhammar, D, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Malfacini, D, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, PM, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, O'Carroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Singh, KD, Smith, CM, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PBMWM, Tirupula, K, Toll, L, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Williams, TL, Woodruff, TM, Yao, C, Ye, RD, Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, AA, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Davies, JA, Abbracchio, MP, Abraham, G, Agoulnik, A, Alexander, W, Al-hosaini, K, Back, M, Baker, JG, Barnes, NM, Bathgate, R, Beaulieu, J-M, Beck-Sickinger, AG, Behrens, M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Brauner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, KJ, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Cox, HM, Csaba, Z, Dahlgren, C, Dent, G, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, Garelja, ML, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gratz, L, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Herr, D, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, Ijzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Larhammar, D, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Malfacini, D, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, PM, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, O'Carroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Singh, KD, Smith, CM, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PBMWM, Tirupula, K, Toll, L, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Williams, TL, Woodruff, TM, Yao, C, and Ye, RD

Abstract

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2023

4. THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

Author

Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, A, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Pawson, AJ, Southan, C, Davies, JA, Abbracchio, MP, Alexander, W, Al-hosaini, K, Baeck, M, Barnes, NM, Bathgate, R, Beaulieu, J-M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Braeuner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, K, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Csaba, Z, Dahlgren, C, Dent, G, Singh, KD, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, IJzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Williams, TL, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, P, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, Ocarroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PMWM, Tirupula, K, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Woodruff, TM, Yao, C, Ye, RD, Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, A, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Pawson, AJ, Southan, C, Davies, JA, Abbracchio, MP, Alexander, W, Al-hosaini, K, Baeck, M, Barnes, NM, Bathgate, R, Beaulieu, J-M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Braeuner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, K, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Csaba, Z, Dahlgren, C, Dent, G, Singh, KD, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, IJzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Williams, TL, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, P, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, Ocarroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PMWM, Tirupula, K, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Woodruff, TM, Yao, C, and Ye, RD

Abstract

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2021

13. Necrosome‐positive granulovacuolar degeneration is associated with TDP‐43 pathological lesions in the hippocampus of ALS/FTLD cases

Author

Van Schoor, E., primary, Koper, M. J., additional, Ospitalieri, S., additional, Dedeene, L., additional, Tomé, S. O., additional, Vandenberghe, R., additional, Brenner, D., additional, Otto, M., additional, Weishaupt, J., additional, Ludolph, A. C., additional, Van Damme, P., additional, Van Den Bosch, L., additional, and Thal, D. R., additional

Published
2020
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21. Necrosome‐positive granulovacuolar degeneration is associated with TDP‐43 pathological lesions in the hippocampus of ALS/FTLD cases.

Author

Van Schoor, E., Koper, M. J., Ospitalieri, S., Dedeene, L., Tomé, S. O., Vandenberghe, R., Brenner, D., Otto, M., Weishaupt, J., Ludolph, A. C., Van Damme, P., Van Den Bosch, L., and Thal, D. R.

Subjects
MOTOR neuron diseases, MOTOR neurons, AMYOTROPHIC lateral sclerosis, RECEPTOR-interacting proteins, FRONTOTEMPORAL lobar degeneration, DNA-binding proteins, SPINAL cord
Abstract

Aim: Granulovacuolar degeneration (GVD) in Alzheimer's disease (AD) involves the necrosome, which is a protein complex consisting of phosphorylated receptor‐interacting protein kinase 1 (pRIPK1), pRIPK3 and phosphorylated mixed lineage kinase domain‐like protein (pMLKL). Necrosome‐positive GVD was associated with neuron loss in AD. GVD was recently linked to the C9ORF72 mutation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with transactive response DNA‐binding protein (TDP‐43) pathology (FTLD‐TDP). Therefore, we investigated whether GVD in cases of the ALS‐FTLD‐TDP spectrum (ALS/FTLD) shows a similar involvement of the necrosome as in AD, and whether it correlates with diagnosis, presence of protein aggregates and cell death in ALS/FTLD. Methods: We analysed the presence and distribution of the necrosome in post‐mortem brain and spinal cord of ALS and FTLD‐TDP patients (n = 30) with and without the C9ORF72 mutation, and controls (n = 22). We investigated the association of the necrosome with diagnosis, the presence of pathological protein aggregates and neuronal loss. Results: Necrosome‐positive GVD was primarily observed in hippocampal regions of ALS/FTLD cases and was associated with hippocampal TDP‐43 inclusions as the main predictor of the pMLKL‐GVD stage, as well as with the Braak stage of neurofibrillary tangle pathology. The central cortex and spinal cord, showing motor neuron loss in ALS, were devoid of any accumulation of pRIPK1, pRIPK3 or pMLKL. Conclusions: Our findings suggest a role for hippocampal TDP‐43 pathology as a contributor to necrosome‐positive GVD in ALS/FTLD. The absence of necroptosis‐related proteins in motor neurons in ALS argues against a role for necroptosis in ALS‐related motor neuron death. [ABSTRACT FROM AUTHOR]

Published
2021
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23. Tau and synuclein pathology in Hereditary Spastic Paraplegia SPG7

Author

Thal, D, Züchner, S, Schulte, C, Schöls, L, Schüle, R, and Synofzik, M

Subjects
ddc: 610, 610 Medical sciences, Medicine, nervous system diseases
Abstract

Objective: SPG7 is one of the most frequent causes of autosomal recessive Hereditary Spastic Paraplegias and spastic ataxias. Ala510Val is the most common mutation, with a frequency of up to 1% in the general population. The exact pathology caused by SPG7 and, in particular, the Ala510Val mutation,[for full text, please go to the a.m. URL], 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Published
2015
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24. Brain infarction, dementia, and related vessel disorders: Impact of infarct size, distribution, and its association with vessel and heart disorders

Author

Hecht, M, Krämer, L, von Arnim, C, Attems, J, Ludolph, A, and Thal, D

Subjects
ddc: 610, mental disorders, cardiovascular system, cardiovascular diseases, 610 Medical sciences, Medicine
Abstract

Objectives: Vascular dementia (VD) can be caused by multiple infarct dementia or strategic infarct dementia. Vascular lesions have been discussed to be associated with Alzheimer's disease (AD). Here, we want to determine the impact of infarct size anddistribution on the degree of dementia, and [for full text, please go to the a.m. URL], 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Published
2015
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27. Large- and Small-Fiber Neuropathy in Patients with Tarlov Cysts

Author

Hulens M, Bruyninckx F, Thal DR, Rasschaert R, Bervoets C, and Dankaerts W

Subjects
perineural cysts, skin biopsies, radicular pain, anal reflex, nerve conduction studies, fibromyalgia, Medicine (General), R5-920
Abstract

Mieke Hulens,1 Frans Bruyninckx,2 Dietmar Rudolf Thal,3,4 Ricky Rasschaert,5 Chris Bervoets,6– 8 Wim Dankaerts1 1Department of Rehabilitation Sciences, Musculoskeletal Rehabilitation Research Unit, Faculty of Kinesiology and Rehabilitation Sciences, KU Leuven, Leuven, Belgium; 2Department of Physical Medicine & Rehabilitation, EMG-Laboratory, University Hospitals of Leuven, Leuven, Belgium; 3Department of Imaging and Pathology, Laboratory of Neuropathology, and Leuven Brain Institute, KU Leuven, Leuven, Belgium; 4Department of Pathology, University Hospitals of Leuven, Leuven, Belgium; 5Department of Neurosurgery, AZ Rivierenland, Bornem, Belgium; 6Department of Neurosciences, Adult Psychiatry, KU Leuven, Leuven, Belgium; 7Department of Ophthalmology, University Hospitals of Leuven, Leuven, Belgium; 8Department Adult Psychiatry, University Psychiatric Center of KU Leuven, Leuven, BelgiumCorrespondence: Mieke HulensDepartment of Rehabilitation Sciences, Musculoskeletal Rehabilitation Research Unit, Faculty of Kinesiology and Rehabilitation Sciences, University of Leuven, Tervuursevest 101, Leuven, Belgium, Tel +32 478 338003, Fax +32 16 32 91 97, Email miekehulens@gmail.comPurpose: Tarlov cysts (TCs) are dilated nerve root sheaths originating from increased cerebrospinal pressure. Patients with TCs often complain of neuropathic pain and paresthesia. The aim of this study was to retrospectively review intraepidermal nerve fiber density (IENFD) and electrodiagnostic (EDX) data from TC patients.Patients and Methods: Lower leg skin biopsy results and EDX data from the L2–S4 myotomes of patients with lumbar or sacral TCs ≥ 8 mm were retrieved from a database of a physical medicine clinic. Patients with compressive pathology, diabetes mellitus and chemotherapy were excluded.Results: IENFD data from 17 patients and EDX data from 24 patients with TCs ≥ 8 mm were available. The mean age was 47 ± 10y, and 83% were women. In 82% of patients, the IENFD was below the 5th percentile by age and sex. EDX showed increased Hoffmann reflex latencies in 25%, increased anal reflex latencies in 95%, and a patchy distribution of neurogenic motor unit potentials in 100%. More than 50% of needle EMG abnormalities appeared in myotomes unrelated to the location of the TCs.Conclusion: Small- and/or large-fiber neuropathy was documented in a significant proportion of patients with TCs. The novel findings may add to the understanding of the mechanisms involved in symptomatic TCs. We propose that pathologically elevated cerebrospinal fluid pressure not only dilates some of the nerve root sheaths to form TCs but also potentially damages axons in nondilated nerve root sheaths and neurons in the dorsal root ganglia.Keywords: perineural cysts, skin biopsies, radicular pain, anal reflex, nerve conduction studies, fibromyalgia

Published
2022

28. EP05.01: Fetal brain maceration score on postmortem MRI versus conventional autopsy.

Author

Hustings, N., Thonissen, Y., Vanderseypen, K., Baldewijns, M., De Catte, L., Thal, D., and Aertsen, M.

Abstract

The purpose of this study is to develop a reproducible brain-specific maceration score on postmortem MRI that correlates well with the signs of brain maceration on fetal autopsy. Conclusions We present a brain-specific post-mortem MRI maceration score that correlates well with the degree of fetal brain maceration seen at histopathological exam. [Extracted from the article]

Published
2022
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30. Accumulation of Marker Protein of DNA damage in humans of the olfactory bulb cells and spinal fluid of Alzheimer Disease Patients

Author

Rudolph, M, Scheithauer, M, von Arnim, C, Begus, Y, Attems, J, Thal, D, Rettinger, G, Zhangfa, S, and Rudolph, KL

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Introduction: The diagnosis of Alzheimer disease (AD) is still challenging and biomarkers for AD remain to be developed. It has been suggested that an analysis of neurons in the olfactory epithelium could help in the diagnosis of AD. On the molecular level there is evidence that DNA damage accumulation[for full text, please go to the a.m. URL], 81. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie

Published
2010
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31. alpha 2-Macroglobulin Inhibits the Malignant Properties of Astrocytoma Cells by Impeding beta-Catenin Signaling

Author

Lindner, I., Hemdan, N.Y.A., Buchold, M., Huse, K., Bigl, M., Oerlecke, I., Ricken, A., Gaunitz, F., Sack, U., Naumann, A., Hollborn, M., Thal, D., Gebhardt, R., Birkenmeier, G., and Publica

Subjects
a2-macroglobulin, human 1321N1 astrocytoma cells, LRP1, glioma, Wnt/ß-catenin pathway
Abstract

Targets that could improve the treatment of brain tumors remain important to define. This study of a transformation-associated isoform of alpha 2-macroglobulin (A2M*) and its interaction with the low-density lipoprotein receptor-related protein-1 (LRP1) suggests a new mechanism for abrogating the malignant potential of astrocytoma cells. LRP1 bound A2M* found to be associated with an inhibition of tumor cell proliferation, migration, invasion, spheroid formation, and anchorage-independent growth. Transcriptional studies implicated effects on the Wnt/beta-catenin signaling pathway. Notably, LRP1 antibodies could phenocopy the effects of A2M*. Our findings suggest a pathway of tumor suppression in astrocytoma that might be tractable to therapeutic exploitation.

Published
2010

32. Assessment of α-Synuclein Pathology

Author

Alafuzoff, I, Parkkinen, L, Al-Sarraj, S, Arzberger, T, Bell, J, Bodi, I, Bogdanovic, N, Budka, H, Ferrer, I, Gelpi, E, Gentleman, S, Giaccone, G, Kamphorst, W, King, A, Korkolopoulou, P, Kovács, G, Larionov, S, Meyronet, D, Monoranu, C, Morris, J, Parchi, P, Patsouris, E, Roggendorf, W, Seilhean, D, Streichenberger, N, Thal, D, and Kretzschmar, H

Abstract

To determine the reliability of assessment of [alpha]-synuclein-immunoreactive ([alpha]S-IR) structures by neuropathologists, 28 evaluators from 17 centers of BrainNet Europe examined current methods and reproducibility of [alpha]S-IR evaluation using a tissue microarray (TMA) technique. Tissue microarray blocks were constructed of samples from the participating centers that contained [alpha]S-IR structures. Slides from these blocks were stained in each center and assessed for neuronal perikaryal inclusions, neurites, and glial cytoplasmic inclusions. The study was performed in 2 phases. First, the TMA slides were stained with the antibody of the center's choice. In this phase, 59% of the sections were of good or acceptable quality, and 4 of 9 antibodies used performed consistently. Differences in interpretation and categorization of [alpha]S-IR structures, however, led to differing results between the laboratories. Prior to the second phase, the neuropathologists participated in a training session on the evaluation of [alpha]S-IR structures. Based on the results of the first phase, selected antibodies using designated antigen retrieval methods were then applied to TMA slides in the second phase. When the designated methods of both staining and evaluation were applied, all 26 subsequently stained TMA sections evaluated were of good/acceptable quality, and a high level of concordance in the assessment of the presence or absence of specific [alpha]S-IR structures was achieved. A semiquantitative assessment of [alpha]S-IR neuronal perikaryal inclusions yielded agreements ranging from 49% to 82%, with best concordance in cortical core samples. These results suggest that rigorous methodology and dichotomized assessment (i.e. determining the presence or absence of [alpha]S-IR) should be applied, and that semiquantitative assessment can be recommended only for the cortical samples. Moreover, the study demonstrates that there are limitations in the scoring of [alpha]S-IR structures.

Published
2008

33. No association of a non-synonymous PLAU polymorphism with Alzheimer's disease and disease-related traits

Author

Papassotiropoulos, A, Tsolaki, M, Wollmer, M A, Molyva, D, Thal, D R, Huynh, K D, Tracy, J, Staehelin, H B, Monsch, A U, Nitsch, R M, Hock, C, University of Zurich, and Papassotiropoulos, A

Subjects
2716 Genetics (clinical), 2738 Psychiatry and Mental Health, Cellular and Molecular Neuroscience, Psychiatry and Mental health, 2804 Cellular and Molecular Neuroscience, 610 Medicine & health, Genetics(clinical), 11359 Institute for Regenerative Medicine (IREM)
Published
2005

34. RESULTS OF THE INTERNATIONAL INTERLABORATORY COMPARISON OF MGMT PROMOTER METHYLATION ANALYSIS INVOLVING TWENTY-THREE ACADEMIC CENTERS IN GERMANY, AUSTRIA AND THE NETHERLANDS

Author

Reifenberger, G., primary, Malzkorn, B., additional, Acker, T., additional, Bettstetter, M., additional, Buslei, R., additional, von Deimling, A., additional, Dietmaier, W., additional, Dubbink, H. J., additional, Eigenbrod, S., additional, Garvalov, B. K., additional, Gerstenmaier, U., additional, Giese, A., additional, Haase, D., additional, Hasselblatt, M., additional, Kirches, E., additional, Koch, A., additional, Marienfeld, R., additional, Mittelbronn, M., additional, Montesinos-Rongen, M., additional, Pagenstecher, A., additional, Riemenschneider, M. J., additional, Prinz, M., additional, Romeike, B., additional, Roos, A., additional, Spiegl-Kreinecker, S., additional, Schittenhelm, J., additional, Schlegel, J., additional, Thal, D. R., additional, Tops, B. B. J., additional, Weis, J., additional, Westphal, G., additional, Worm, K., additional, and Felsberg, J., additional

Published
2014
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35. Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism

Author

Papassotiropoulos, A, Streffer, J R, Tsolaki, M, Schmid, S, Thal, D, Nicosia, F, Iakovidou, V, Maddalena, A, Lütjohann, D, Ghebremedhin, E, Hegi, T, Pasch, T, Träxler, M, Brühl, A, Benussi, L, Binetti, G, Braak, H, Nitsch, R M, Hock, C, University of Zurich, and Papassotiropoulos, A

Subjects
2728 Neurology (clinical), 1201 Arts and Humanities (miscellaneous), 610 Medicine & health, 11359 Institute for Regenerative Medicine (IREM)
Published
2003

36. The need to unify neuropathological assessments of vascular alterations in the ageing brain : Multicentre survey by the BrainNet Europe consortium

Author

Alafuzoff, Irina, Gelpi, E., Al-Sarraj, S., Arzberger, T., Attems, J., Bodi, I., Bogdanovic, N., Budka, H., Bugiani, O., Englund, E., Ferrer, I., Gentleman, S., Giaccone, G., Graeber, M. B., Hortobagyi, T., Höftberger, R., Ironside, J. W., Jellinger, K., Kavantzas, N., King, A., Korkolopoulou, P., Kovács, G. G., Meyronet, D., Monoranu, C., Parchi, P., Patsouris, E., Roggendorf, W., Rozemuller, A., Seilhean, D., Streichenberger, N., Thal, D. R., Wharton, S. B., Kretzschmar, H., Alafuzoff, Irina, Gelpi, E., Al-Sarraj, S., Arzberger, T., Attems, J., Bodi, I., Bogdanovic, N., Budka, H., Bugiani, O., Englund, E., Ferrer, I., Gentleman, S., Giaccone, G., Graeber, M. B., Hortobagyi, T., Höftberger, R., Ironside, J. W., Jellinger, K., Kavantzas, N., King, A., Korkolopoulou, P., Kovács, G. G., Meyronet, D., Monoranu, C., Parchi, P., Patsouris, E., Roggendorf, W., Rozemuller, A., Seilhean, D., Streichenberger, N., Thal, D. R., Wharton, S. B., and Kretzschmar, H.

Abstract

Here, we summarise the results after carrying out a large survey regarding the assessment of vascular alterations, both vessel changes and vascular lesions in an inter-laboratory setting. In total, 32 neuropathologists from 22 centres, most being members of BrainNet Europe (BNE), participated by filling out a questionnaire with emphasis on assessment of common vascular alterations seen in the brains of aged subjects. A certain level of harmonisation has been reached among BNE members regarding sectioning of the brain, harvesting of brain tissue for histology and staining used when compared to the survey carried out in 2006 by Pantoni and colleagues. The most significant variability was seen regarding the assessment of severity and of clinical significance of vascular alterations. Two strategies have recently been recommended regarding the assessment of vascular alterations in aged and demented subjects. The National Institute on Aging - Alzheimer's Association (NIA-AA) recommends the assessment of hippocampal sclerosis, vascular brain injury and microvascular lesions in 12 regions. Although this strategy will be easy to follow, the recommendations do not inform how the load of observed alterations should be assessed and when the observed lesions are of significance. Deramecourt and his colleagues recommend an assessment and semiquantitative grading of various pathologies in 4 brain regions. This strategy yielded a total score of 0 to 20 as an estimate of pathology load. It is, however, not clear which score is considered to be of clinical significance. Furthermore, in several BNE trials the semiquantitative assessment has yielded poor agreement rates; an observation that might negatively influence the strategy proposed by Deramecourt and his colleagues. In line with NIA-AA, a dichotomised approach of easily recognisable lesions in a standardised set of brain regions harvested for neuropathological assessment and applying reproducible sampling and staining strategies

Published
2012
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39. Association study of cholesterol-related genes in Alzheimer's disease

Author

Wollmer, M A, Sleegers, K, Ingelsson, M, Zekanowski, C, Brouwers, N, Maruszak, A, Brunner, F, Huynh, K D, Kilander, L, Brundin, R M, Hedlund, M, Giedraitis, V, Glaser, A, Engelborghs, S, De Deyn, P P, Kapaki, E, Tsolaki, M, Daniilidou, M, Molyva, D, Paraskevas, G P, Thal, D R, Barcikowska, M, Kuznicki, J, Lannfelt, L, Van Broeckhoven, C, Nitsch, R M, Hock, C, Papassotiropoulos, A, Wollmer, M A, Sleegers, K, Ingelsson, M, Zekanowski, C, Brouwers, N, Maruszak, A, Brunner, F, Huynh, K D, Kilander, L, Brundin, R M, Hedlund, M, Giedraitis, V, Glaser, A, Engelborghs, S, De Deyn, P P, Kapaki, E, Tsolaki, M, Daniilidou, M, Molyva, D, Paraskevas, G P, Thal, D R, Barcikowska, M, Kuznicki, J, Lannfelt, L, Van Broeckhoven, C, Nitsch, R M, Hock, C, and Papassotiropoulos, A

Abstract

Alzheimer's disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P < or = 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples.

Published
2007

40. Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's disease

Author

Papassotiropoulos, A, Lambert, J C, Wavrant-De Vrièze, F, Wollmer, M A, von der Kammer, H, Streffer, J R, Maddalena, A, Huynh, K D, Wolleb, S, Lütjohann, D, Schneider, B, Thal, D R, Grimaldi, L M E, Tsolaki, M, Kapaki, E, Ravid, R, Konietzko, U, Hegi, T, Pasch, T, Jung, H, Braak, H, Amouyel, P, Rogaev, E I, Hardy, J, Hock, C, Nitsch, R M, Papassotiropoulos, A, Lambert, J C, Wavrant-De Vrièze, F, Wollmer, M A, von der Kammer, H, Streffer, J R, Maddalena, A, Huynh, K D, Wolleb, S, Lütjohann, D, Schneider, B, Thal, D R, Grimaldi, L M E, Tsolaki, M, Kapaki, E, Ravid, R, Konietzko, U, Hegi, T, Pasch, T, Jung, H, Braak, H, Amouyel, P, Rogaev, E I, Hardy, J, Hock, C, and Nitsch, R M

Abstract

Alzheimer's disease (AD) is the most common cause of dementia. It is characterized by beta-amyloid (A beta) plaques, neurofibrillary tangles and the degeneration of specifically vulnerable brain neurons. We observed high expression of the cholesterol 25-hydroxylase (CH25H) gene in specifically vulnerable brain regions of AD patients. CH25H maps to a region within 10q23 that has been previously linked to sporadic AD. Sequencing of the 5' region of CH25H revealed three common haplotypes, CH25Hchi2, CH25Hchi3 and CH25Hchi4; CSF levels of the cholesterol precursor lathosterol were higher in carriers of the CH25Hchi4 haplotype. In 1,282 patients with AD and 1,312 healthy control subjects from five independent populations, a common variation in the vicinity of CH25H was significantly associated with the risk for sporadic AD (p = 0.006). Quantitative neuropathology of brains from elderly non-demented subjects showed brain A beta deposits in carriers of CH25Hchi4 and CH25Hchi3 haplotypes, whereas no A beta deposits were present in CH25Hchi2 carriers. Together, these results are compatible with a role of CH25Hchi4 as a putative susceptibility factor for sporadic AD; they may explain part of the linkage of chromosome 10 markers with sporadic AD, and they suggest the possibility that CH25H polymorphisms are associated with different rates of brain A beta deposition.

Published
2005

41. Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease

Author

Watabe-Rudolph, M., primary, Song, Z., additional, Lausser, L., additional, Schnack, C., additional, Begus-Nahrmann, Y., additional, Scheithauer, M.- O., additional, Rettinger, G., additional, Otto, M., additional, Tumani, H., additional, Thal, D. R., additional, Attems, J., additional, Jellinger, K. A., additional, Kestler, H. A., additional, von Arnim, C. A. F., additional, and Rudolph, K. L., additional

Published
2012
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42. Transgenic Expression of Intraneuronal A 42 But Not A 40 Leads to Cellular A Lesions, Degeneration, and Functional Impairment without Typical Alzheimer's Disease Pathology

Author

Abramowski, D., primary, Rabe, S., additional, Upadhaya, A. R., additional, Reichwald, J., additional, Danner, S., additional, Staab, D., additional, Capetillo-Zarate, E., additional, Yamaguchi, H., additional, Saido, T. C., additional, Wiederhold, K.-H., additional, Thal, D. R., additional, and Staufenbiel, M., additional

Published
2012
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44. Loss of -Secretase Function Impairs Endocytosis of Lipoprotein Particles and Membrane Cholesterol Homeostasis

Author

Tamboli, I. Y., primary, Prager, K., additional, Thal, D. R., additional, Thelen, K. M., additional, Dewachter, I., additional, Pietrzik, C. U., additional, St. George-Hyslop, P., additional, Sisodia, S. S., additional, De Strooper, B., additional, Heneka, M. T., additional, Filippov, M. A., additional, Muller, U., additional, van Leuven, F., additional, Lutjohann, D., additional, and Walter, J., additional

Published
2008
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46. ROLE OF PRESENILINS IN LIPID HOMEOSTASIS

Author

Luetjohann, D., primary, Tamboli, I., additional, Prager, K., additional, Thal, D., additional, Thelen, K., additional, Wahle, T., additional, Breiden, B., additional, Sandhoff, K., additional, Leuven, F. van, additional, and Walter, J., additional

Published
2008
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48. Pathological consequences of VCP mutations on human striated muscle

Author

Hubbers, C. U., primary, Clemen, C. S., additional, Kesper, K., additional, Boddrich, A., additional, Hofmann, A., additional, Kamarainen, O., additional, Tolksdorf, K., additional, Stumpf, M., additional, Reichelt, J., additional, Roth, U., additional, Krause, S., additional, Watts, G., additional, Kimonis, V., additional, Wattjes, M. P., additional, Reimann, J., additional, Thal, D. R., additional, Biermann, K., additional, Evert, B. O., additional, Lochmuller, H., additional, Wanker, E. E., additional, Schoser, B. G. H., additional, Noegel, A. A., additional, and Schroder, R., additional

Published
2007
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