AZNeuro

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AZNeuro Publications

25th November 2019

Efficacy and Safety of Lanabecestat for Treatment of Early and Mild Alzheimer Disease The AMARANTH and DAYBREAK-ALZ Randomized Clinical Trials

Journal: JAMA NEUROLOGY
Authors: Alette M. Wessels, PhD; Pierre N. Tariot, MD; Jennifer A. Zimmer, MD; Katherine J. Selzler, PhD; Sonja M. Bragg, MPH; Scott W. Andersen, MS; John Landry, MMath; James H. Krull, PharmD; AnnCatherine M. Downing, PharmD; Brian A. Willis, PhD; Sergey Shcherbinin, PhD; Jamie Mullen, MD; Peter Barker, PhD; Jennifer Schumi, PhD; Craig Shering, DPhil; Brandy R. Matthews, MD; Robert A. Stern, PhD; Bruno Vellas, MD; Sharon Cohen, MD; Emer MacSweeney, FRCR; Mercè Boada, MD; John R. Sims, MD
Collaborator: 1Eli Lilly and Company, Indianapolis, Indiana 2Banner Alzheimer’s Institute, University of Arizona College of Medicine, Phoenix 3AstraZeneca, Waltham, Massachusetts, and Gaithersburg, Maryland 4Now retired 5Alzheimer’s Disease Center, Boston University School of Medicine, Boston, Massachusetts 6Gérontopôle, Centre Hospitalier Universitaire de Toulouse, Unités Mixtes de Recherche Institut National de la Santé et de la Recherche Médicale 1027, Université Toulouse III–Paul Sabatier, Toulouse, France 7Toronto Memory Program, Toronto, Ontario, Canada 8Re:Cognition Health, London, United Kingdom 9Research Center and Memory Clinic, Fundació Alzheimer Centre Educacional, Institut Català de Neurociències Aplicades, Barcelona–Universitat Internacional de Catalunya, Barcelona, Spain 10Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain

21st October 2019

Preclinical development of a high affinity alpha-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular alpha-synuclein and attenuate pathological alpha-synuclein spreading in vivo

Journal: Neurobiology of Disease
Authors: Schofield DJ, Irving L, Calo L, Bogstedt A, Rees G, Nuccitelli A, Narwal R, Petrone M, Roberts J, Cusdin F, Dosanjh B, Lloyd C, Dobson C, Gurrell I, McFarlane M, Rockenstein E, Spencer B, Masliah E, Grazia Spillantini M, Tan K, Billinton A, Vaughan T, Chessell I, Perkinton MS
Collaborator: University of California, San Diego, University of Cambridge

1st July 2019

Soluble tau aggregates inhibit synaptic long-term depression and amyloid ß-facilitated LTD in vivo

Journal: Neurobiology of Disease
Authors: Ondrejcak T, Hu NW, Corbett GT, Fraser G, Perkinton MS, Walsh DM, Billinton A, Rowan MJ
Collaborator: Trinity College Dublin, Brigham and Women's Hospital

1st September 2019

Antibodies binding the head domain of P2X4 inhibit channel function and reverse neuropathic pain

Journal: PAIN
Authors: Williams WA, Linley JE, Jones CA, Shibata Y, Snijder A, Button J, Hatcher JP, Huang L, Taddese B, Thornton P, Schofield DJ, Thom G, Popovic B, Dosanjh B, Wilkinson T, Hughes J, Dobson CL, Groves MA, Webster CI, Billinton A, Vaughan TJ, Chessell I

4th November 2019

Opportunities and challenges in phenotypic screening for neurodegenerative disease research

Journal: Journal of Medicinal Chemistry
Authors: Brown DG, Wobst HJ

16th July 2019

Identification of a core amino acid motif within the  subunit of GABAARs that promotes inhibitory synaptogenesis and resilience to seizures

Journal: Cell Reports
Authors: Nathanson AJ, Zhang Y, Smalley JL, Ollerhead TA, Santos MAR, Andrews PM, Bope C, Brandon NJ, Hines RM, Davies PA, Moss SJ
Collaborator: Tufts University

26th June 2019

Non-invasive mechanical joint loading as an alternative model for osteoarthritic pain

Journal: Arthritis & Rheumatology
Authors: Heegde F, Luiz AP, Santana-Varela S, Chessel IP, Welsh F, Wood JN, Chenu C
Collaborator: University College London, RVC London

23rd August 2019

PDE10A mutations help to unwrap the neurobiology of hyperkinetic disorders

Journal: Cellular Signalling
Authors: Whiteley E, Tejeda G, Baillie GS, Brandon NJ

1st June 2018

Extracellular monomeric and aggregated tau efficiently enter human neurons through overlapping but distinct pathways

Journal: Cell Reports
Authors: Wassmer T, Evans L, Fraser G, Smith J, Perkinton MS, Billinton A, Livesey FJ
Relevant Pages: 3624

21st May 2018

Differential pharmacology and binding of mGlu2 allosteric modulators

Journal: Molecular Pharmacology
Authors: O’Brien WE, Shaw DM, Cho HP, Cross AJ, Wesolowski SS, Felts AS, Bergare J, Elmore CS, Lindsley CW, Niswender CM, Conn PJ
Relevant Pages: 526-540

5th May 2018

Development and genetic regulation of the human frontal cortex transcriptiome in schizophrenia

Journal: Neuron
Authors: Jaffe A, Straub R, Shin J, Tao R, Gao Y, Collado Torres L, Kam-Thong T, Xi S, Quan J, Colantuoni C, Ulrich B, Maher B, Deep-Soboslay A, Cross AJ, Brandon NJ, Leek J, Hyde T, Kleinman J, Weinberger DJ
Relevant Pages: doi:10.1038/nn.4181

13th April 2018

Small RNAs may answer big questions in mental illness

Journal: Biological Psychiatry
Authors: Wright C, Ross DA, Weinberger D
Relevant Pages: e1–e3

11th April 2018

Interleukin-33 is activated by allergen- and necrosis-associated proteolytic activities to regulate its alarmin activity during epithelial damage

Journal: Scientific Reports
Authors: Scott IC, Majithiya JB, Sanden C, Thornton P, Sanders P, Moore T, Guscott M, Corkill DJ, Erjefalt JS, Cohen ES
Relevant Pages: doi:10.1038/s41598-018-21589-2

26th March 2018

Metabotropic glutamate receptor 2/3 as targets for treating nicotine addiction

Journal: Biological Psychiatry
Authors: Cross AJ, Anthenelli R, Li X
Relevant Pages: 947–954

21st March 2018

Toward β-secretase-1 inhibitors with improved isoform selectivity

Journal: Journal of Medicinal Chemistry
Authors: Johansson P, Kaspersson K, Gurrell I, Bäck E, Eketjäll S, Scott C, Cebers G, Thorne P, McKenzie M, Beaton H, Davey P, Kolmodin K, Holenz J, Duggan ME, Häberlein SB, Bürli RW
Relevant Pages: 3491–3502

20th March 2018

FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system

Journal: Molecular Psychiatry
Authors: Yalla K, Elliott C, Day JP, Findlay J, Barratt S, Hughes ZA, Wilson L, Whiteley E, Popiolek M, Li Y, Dunlop J, Killick R, Adams DR, Brandon NJ, Houslay MD, Hao B, Baillie GS
Relevant Pages: 1278–1286

19th March 2018

Small molecule inducers of ABCA1 and apoE that act though indirect activation of the LXR pathway

Journal: Journal of Lipid Research
Authors: Fan J, Zhao RQ, Parro C, Zhao W, Chou H-Y, Robert J, Deeb TZ, Barichievy S, Brandon NJ, Wood MW, Kulic I, Wellington CL
Relevant Pages: 830-842

1st March 2018

Central inhibition of granulocyte-macrophage colony-stimulating factor is analgesic in experimental neuropathic pain

Journal: Pain
Authors: Nicol LSC, Thornton P, Hatcher JP, Glover CP, Webster CI, Burrell M, Hammett K, Jones CA, Sleeman MA, Billinton A, Chessell I
Relevant Pages: 532

21st February 2018

Clinical bioavailability of the novel BACE1 inhibitor lanabecestat (AZD3293): Assessment of tablet formulations versus an oral solution and the impact of gastric pH on pharmacokinetics

Journal: Clinical Pharmacology in Drug Development
Authors: Ye N, Monk SA, Daga P, Bender DM, Rosen LB, Mullen J, Minkwitz MC, Kugler AR
Relevant Pages: 233-243

21st February 2018

Isolation of blood-brain barrier-crossing antibodies from a phage display library by competitive elution and their ability to penetrate the central nervous system

Journal: mAbs Journal
Authors: Thom G, Hatcher JP, Hearn A, Paterson J, Rodrigo N, Beljean A, Gurrell I, Webster CI
Relevant Pages: 304-314

30th January 2018

Extracellular monomeric and aggregated tau efficiently enter human neurons through overlapping but distinct pathways

Journal: Cell Reports
Authors: Wassmer T, Evans L, Fraser G, Smith J, Perkinton MS, Billinton A, Livesey FJ

19th December 2017

28th November 2017

Molecular architecture of potassium chloride co-transporter KCC2

Journal: Scientific Reports
Authors: Fan J, Zhao RQ, Parro C, Zhao W, Chou H-Y, Robert J, Deeb TZ, Barichievy S, Brandon NJ, Wood MW, Kulic I, Wellington CL, Moss SJ
Relevant Pages: 1038

21st November 2017

Metabotropic glutamate receptors 2 and 3 as targets for treating nicotine addiction

Journal: Biological Psychiatry
Authors: Jaffe A, Straub R, Shin J, Tao R, Gao Y, Collado Torres L, Kam-Thong T, Xi S, Quan J, Colantuoni C, Ulrich B, Maher B, Deep-Soboslay A, Cross AJ, Brandon NJ, Leek J, Hyde T, Kleinman J, Weinberger DJ
Relevant Pages: 947–954

8th November 2017

X-ray characterization and structure-based optimization of striatal-enriched protein tyrosine phosphatase inhibitors

Journal: Journal of Medicinal Chemistry
Authors: Witten MR, Wissler L, Snow M, Geschwindner S, Read JA, Brandon NJ, Nairn AC, Lombroso PJ, Käck H, Ellman JA
Relevant Pages: 9299–9319

24th October 2017

Challenges in the development of an M4 PAM preclinical candidate: The discovery, SAR, and biological characterization of a series of azetidine-derived tertiary amides

Journal: Bioorganic & Medicinal Chemistry Letters
Authors: Johansson P, Kaspersson K, Gurrell I, Bäck E, Eketjäll E, Engers DW, Scott C, Cebers G, Thorne P, McKenzie M, Beaton H, Davey P, Melancon BJ, Tarr JC, Noetzel MJ, Niswender CM, Kolmodin K, Lindsley CW, Luscombe VB, Holenz J, Duggan ME, Häberlein SB, Bürli RW
Relevant Pages: 5179-5184

23rd October 2017

Molecular-based diagnosis of Multiple Sclerosis and its progressive stage

Journal: Annals of Neurology
Authors: Barbour C, Kosa P, Komori M, Tanigawa M, Masvekar R, Wu T, Johnson K, Douvaras P, Fossati V, Herbst R, Wang Y, Tan K, Greenwood M, Bielekova B

16th October 2017

Estradiol modulates the efficacy of fast synaptic inhibition by decreasing the dwell time of GABAA receptors at inhibitory synapses

Journal: Proceedings of the National Academy of Sciences of the United States of America
Authors: Fan J, Zhao RQ, Parro C, Zhao W, Chou H-Y, Robert J, Deeb TZ, Barichievy S, Brandon NJ, Wood MW, Kulic I, Wellington CL, Moss SJ
Relevant Pages: 8424

1st October 2017

Central and peripheral circadian clocks and their role in Alzheimer’s disease

Journal: Disease Models & Mechanisms
Authors: Chauhan R, Chen KF, Kent BA, Crowther DC

21st September 2017

Current understanding of PDE10A in the modulation of basal ganglia circuitry

Journal: Book
Authors: Schuelke J, Brandon NJ
Relevant Pages: 1

20th September 2017

ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy

Journal: Nature
Authors: Shi Y, Yamada K, Liddelow S, Smith S, Zhao L, Luo W, Tsai R, Spina S, Grinberg L, Rojas J, Gallardo G, Wang K, Roh J, Robinson G, Finn MB, Jiang H, Sullivan P Baufeld C, Wood MW, Sutphen C, McCue L, Xiong C, Del-Aguila J, Morris J, Cruchaga C, Alzheimer’s Disease Neuroimaging Initiative, Fagan A, Miller B, Boxer A, Seely W, Butovsky O, Barres B, Paul S, Holtzman D
Relevant Pages: 549

30th August 2017

TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer’s disease-associated H157Y variant

Journal: EMBO Molecular Medicine
Authors: Thornton P, Sevalle J, Deery MJ, Fraser G, Zhou Y, Ståhl S, Franssen EH, Dodd RB, Qamar SG, Gomez Perez-Nievas B, Nicol LSC, Eketjäll S, Revell J, Jones CA, Billinton A, St George-Hyslop PH, Chessell I, Crowther DC
Relevant Pages: 1366-1378

10th August 2017

Seizing control of KCC2: A new therapeutic target for epilepsy

Journal: Trends in Neurosciences
Authors: Mukherjee J, Cardarelli RW, Cantaut-Belarif Y, Deeb TZ, Srivastava D, Pangalos M, Triller A, Maguire, Brandon N, Moss SZ
Relevant Pages: 555–571

17th July 2017

Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M4 PAM VU0467154

Journal: Neuropharmacology
Authors: Gould RW, Grannan MD, Gunter BW, Ball J, Bubser M, Bridges TM, Wess J, Wood MW, Brandon NJ, Duggan ME, Niswender CM, Lindsley CW, Conn PJ, Jones CK
Relevant Pages: 492-502

1st July 2017

TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer’s disease-associated H157Y variant

Journal: EMBO molecular medicine
Authors: Thornton P, Sevalle J, Fraser G, Zhou Y, Ståhl S, Elske H, Dodd RB, Qamar SG, Gomez Perez-Nievas B, Eketjäll S, Revell J, Billinton A, St George-Hyslop PH, Chessell I, Crowther DC
Relevant Pages: e201707673

16th June 2017

N-ethylmaleimide increases KCC2 activity by modulating transporter phosphorylation

Journal: Gordon Research Conference - Inhibition in the CNS 2017
Authors: Conway LC, Cardarelli RA, Moore YE, Jones K, McWilliams LJ, Baker DJ, Burnham MP, Bürli RW, Wang Q, Brandon NJ, Moss SJ, Deeb TZ

13th June 2017

Broad analgesic activity of a novel, selective M1 agonist

Journal: Neuropharmacology
Authors: Wood MW, Martino G, Coupal M, Lindberg M, Schroeder P, Santhakumar V, Valiquette M, Sandin J, Widzowski D, Laird J
Relevant Pages: 233-241

20th May 2017

Isolation and cultivation of primary brain endothelial cells from adult mice

Journal: Bio-protocol
Authors: Assmann JC, Müller K, Wenzel J, Walther T, Brands J, Thornton P, Allan SM, Schwaninger M
Relevant Pages: e2294

6th May 2017

Challenges in development of an M4 PAM preclinical candidate: The discovery, SAR, and in vivo characterization of a series of 3-aminoazetidine-derived amides

Journal: Bioorganic & Medicinal Chemistry Letters
Authors: Johansson P, Kaspersson K, Gurrell I, Bäck E, Eketjäll E, Scott C, Cebers G, Thorne P, McKenzie M, Beaton H, Melancon BJ, Weiner RL, Nance KD, Noetzel MJ, Tarr JC, Niswender CM, Luscombe VB, Davey P, Lindsley CW, Kolmodin K, Holenz J, Duggan ME, Häberlein SB, Bürli RW
Relevant Pages: 2990-2995

26th April 2017

Structural insight into allosteric modulation of protease-activated receptor 2

Journal: Nature
Authors: Cheng RKY, Fiez-Vandal C, Schlenker O, Edman K, Aggeler B, Brown D, Brown G, Cooke R, Dumelin C, Dore AS, Geschwindner S, Grebner C, Hermansson N-O, Jazayeri A, Johansson P, Leong L, Prihandoko R, Rappas M, SOutter H, Snijder A, Sundstrom L, Tehan B, Thornton P, Troast D, Wiggin G, Zhukov A, Marshall FH, Dekker N
Relevant Pages: 112-115

24th April 2017

Wild-type, but not mutant N296H, human tau restores Aβ-mediated inhibition of LTP in Tau−/− mice

Journal: Frontiers in Neuroscience
Authors: Vargas-Caballero M, Denk F, Wobst HJ, Arch E, Pegasiou CM, Oliver PL, Shipton OA, Paulsen O, Wade-Martins R

13th April 2017

Optimization of M4 positive allosteric modulators (PAMs): The discovery of VU0476406, a non-human primate in vivo tool compound for translational pharmacology

Journal: Bioorganic & Medicinal Chemistry Letters
Authors: Melancon BJ, Wood MR, Noetzel MJ, Nance KD, Engelber EM, Han C, Lamsal A, Chang S, Cho HP, Byers FW, Bubser M, Jones CK, Niswender CM, Wood MW, Engers DW, Wu D, Brandon NJ, Duggan ME, Conn PJ, Bridges TM, Lindsley CW
Relevant Pages: 2296-2301

22nd March 2017

Biomarker of extracellular matrix remodelling C1M and proinflammatory cytokine interleukin 6 are related to synovitis and pain in end-stage knee osteoarthritis patients

Journal: Pain
Authors: Radojčić M, Thudium C, Henriksen K, Tan K, Karlsten R, Dudley A, Chessell I, Karsdal M, Bay-Jensen A-C, Crema M, Guermazi A
Relevant Pages: 1254–1263

16th March 2017

Membrane association and release of wild-type and pathological tau from organotypic brain slice cultures

Journal: Cell Death & Disease
Authors: Wassmer T, Evans L, Fraser G, Smith J, Perkinton MS, Billinton A, Livesey FJ
Relevant Pages: e2671

13th March 2017

Protein misfolding in neurodegenerative diseases: implications and strategies

Journal: Translational Neurodegeneration
Authors: Sweeney P, Park H, Baumann M, Dunlop J, Frydman J, Kopito R, McCampbell A, Leblanc G, Venkateswaran A, Nurmi A, Hodgson R
Relevant Pages: 6:6

9th March 2017

Utility of an APP-GAL4 reporter assay to identify early neuronal responses to beta-gamma-secretase APP processing reveals impaired AKT signaling and upregulation of FOXO3a

Journal: Molecular Neurodegeneration
Authors: Wassmer T, Evans L, Fraser G, Smith J, Perkinton MS, Billinton A, Livesey FJ, Williams RJ
Relevant Pages: 673-68

2nd March 2017

Substrate and method dependent inhibition of three ABC-transporters (MDR1, BCRP, and MRP2)

Journal: European Journal of Pharmaceutical Sciences
Authors: Pedersen J, Khan EK, Bergstrom CAS, Palm J, Hoogstraate J, Artursson P
Relevant Pages: 70-76

17th February 2017

Deficits in the activity of presynaptic γ-Aminobutyric acid type B receptors contribute to altered neuronal excitability in Fragile X Syndrome

Journal: The Journal of Biological Chemistry
Authors: Fan J, Zhao RQ, Parro C, Zhao W, Chou H-Y, Robert J, Deeb TZ, Barichievy S, Brandon NJ, Wood MW, Kulic I, Wellington CL, Moss SJ
Relevant Pages: 6621-6632

31st January 2017

The impact of disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: a systematic review

Journal: Translational Psychiatry
Authors: Dahoun T, Trossbach S, Brandon N, Korth C, Howes O
Relevant Pages: e1015

12th January 2017

Cytoplasmic relocalization of TAR DNA-binding protein 43 is not sufficient to reproduce cellular pathologies associated with ALS in vitro

Journal: Frontiers in Molecular Neuroscience
Authors: Wobst HJ, Wesolowski SS, Delsing L, Jacobsen S, Deeb TZ, Dunlop J, Brandon NJ, Moss SJ

24th December 2016

GABA receptor occupancy by subtype selective GABA modulators: PET studies in humans

Journal: Psychopharmacology
Authors: Jaffe A, Straub R, Shin J, Tao R, Gao Y, Collado Torres L, Kam-Thong T, Xi S, Quan J, Colantuoni C, Ulrich B, Maher B, Deep-Soboslay A, Cross AJ, Brandon NJ, Leek J, Hyde T, Kleinman J, Weinberger DJ
Relevant Pages: 707–716

20th December 2016

From bench to bedside: mGluR2 positive allosteric modulators as medications to treat substance use disorders

Journal: Psychopharmacology
Authors: Acri J, Cross AJ, Skolnick P
Relevant Pages: 1347–1355

19th December 2016

Enhanced delivery of IL-1 receptor antagonist to the CNS as a novel anti-TfR-IL-1RA fusion reverses neuropathic mechanical hypersensitivity

Journal: Pain
Authors: Webster CI, Hatcher JP, Burrell M, Thom G, Thornton P, Gurrell I, Chessell I
Relevant Pages: 660–668

16th December 2016

Discovery of VU0467485/AZ13713945: An M4 positive allosteric modulator evaluated as a preclinical candidate for the treatment of Schizophrenia

Journal: ACS Medicinal Chemistry Letters
Authors: Melancon BJ, Wood MR, Noetzel MJ, Nance KD, Engelber EM, Han C, Lamsal A, Chang S, Cho HP, Byers FW, Bubser M, Jones CK, Niswender CM, Wood MW, Engers DW, Wu D, Brandon NJ, Duggan ME, Conn PJ, Bridges TM, Lindsley CW
Relevant Pages: 233–238

30th November 2016

Challenges in the development of an M4 PAM in vivo tool compound: The discovery of VU0467154 and unexpected DMPK profiles of close analogs

Journal: Bioorganic & Medicinal Chemistry Letters
Authors: Melancon BJ, Wood MR, Noetzel MJ, Nance KD, Engelber EM, Han C, Lamsal A, Chang S, Cho HP, Byers FW, Bubser M, Jones CK, Niswender CM, Wood MW, Engers DW, Wu D, Brandon NJ, Duggan ME, Conn PJ, Bridges TM, Lindsley CW
Relevant Pages: 171-175

2nd November 2016

Adjunctive lanicemine (AZD6765) in patients with major depressive disorder and history of inadequate response to antidepressants: a randomized, placebo-controlled study

Journal: Neuropsychopharmacology
Authors: Gerard Sanacora, Michael R Johnson, Arif Khan, Sarah D Atkinson, Robert R Riesenberg, Juan P Schronen, Michael A Burke, John M Zajecka, Luis Barra, Hong-Lin Su, Joel A Posener, Khanh H Bui, Michael C Quirk, Timothy M Piser, Sanjay J Mathew & Sanjeev Pathak
Relevant Pages: 844–853

6th February 2014

The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease

Journal: Disease Models & Mechanisms
Authors: Chen KF, Possidente B, Lomas DA, Crowther DC
Relevant Pages: 7(4), 445-458

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