Central nervous system myeloid cells as drug targets: current status and translational challenges

被引:92
作者
Biber, Knut [1 ,4 ]
Moeller, Thomas [2 ,3 ]
Boddeke, Erik [4 ]
Prinz, Marco [5 ,6 ]
机构
[1] Univ Freiburg, Sect Mol Psychiat, Dept Psychiat & Psychotherapy, D-79104 Freiburg, Germany
[2] Lundbeck Res USA, Neuroinflammat Dis Biol Unit, Paramus, NJ 07652 USA
[3] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA
[4] Univ Groningen, Univ Med Ctr Groningen, Sect Med Physiol, Dept Neurosci, NL-9713 Groningen, Netherlands
[5] Univ Freiburg, Inst Neuropathol, Hugstetter Str 55, D-79106 Freiburg, Germany
[6] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79104 Freiburg, Germany
关键词
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TRANSGENIC MOUSE MODEL; WILD-TYPE MICROGLIA; PURINERGIC P2X(7) RECEPTOR; MARROW-DERIVED MICROGLIA; HUMAN ALZHEIMERS-DISEASE; BETA-AMYLOID DEPOSITION; ALPHA-INDUCED CHANGES; CNS GLIAL MODULATOR; IN-VITRO EVIDENCE;
D O I
10.1038/nrd.2015.14
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Myeloid cells of the central nervous system (CNS), which include parenchymal microglia, macrophages at CNS interfaces and monocytes recruited from the circulation during disease, are increasingly being recognized as targets for therapeutic intervention in neurological and psychiatric diseases. The origin of these cells in the immune system distinguishes them from ectodermal neurons and other glia and endows them with potential drug targets distinct from classical CNS target groups. However, despite the identification of several promising therapeutic approaches and molecular targets, no agents directly targeting these cells are currently available. Here, we assess strategies for targeting CNS myeloid cells and address key issues associated with their translation into the clinic.
引用
收藏
页码:110 / 124
页数:15
相关论文
共 271 条
[1]   Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2 [J].
Abbadie, C ;
Lindia, JA ;
Cumiskey, AM ;
Peterson, LB ;
Mudgett, JS ;
Bayne, EK ;
DeMartino, JA ;
MacIntyre, DE ;
Forrest, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (13) :7947-7952
[2]   An Effector-Reduced Anti-β-Amyloid (Aβ) Antibody with Unique Aβ Binding Properties Promotes Neuroprotection and Glial Engulfment of Aβ [J].
Adolfsson, Oskar ;
Pihlgren, Maria ;
Toni, Nicolas ;
Varisco, Yvan ;
Buccarello, Anna Lucia ;
Antoniello, Katia ;
Lohmann, Sophie ;
Piorkowska, Kasia ;
Gafner, Valerie ;
Atwal, Jasvinder K. ;
Maloney, Janice ;
Chen, Mark ;
Gogineni, Alvin ;
Weimer, Robby M. ;
Mortensen, Deborah L. ;
Friesenhahn, Michel ;
Ho, Carole ;
Paul, Robert ;
Pfeifer, Andrea ;
Muhs, Andreas ;
Watts, Ryan J. .
JOURNAL OF NEUROSCIENCE, 2012, 32 (28) :9677-9689
[3]   Local self-renewal can sustain CNS microglia maintenance and function throughout adult life [J].
Ajami, Bahareh ;
Bennett, Jami L. ;
Krieger, Charles ;
Tetzlaff, Wolfram ;
Rossi, Fabio M. V. .
NATURE NEUROSCIENCE, 2007, 10 (12) :1538-1543
[4]   Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool [J].
Ajami, Bahareh ;
Bennett, Jami L. ;
Krieger, Charles ;
McNagny, Kelly M. ;
Rossi, Fabio M. V. .
NATURE NEUROSCIENCE, 2011, 14 (09) :1142-U263
[5]   Pharmacokinetic and pharmacodynamic profiling of a P2X7 receptor allosteric modulator GSK1482160 in healthy human subjects [J].
Ali, Zahid ;
Laurijssens, Bart ;
Ostenfeld, Thor ;
McHugh, Simon ;
Stylianou, Anastasia ;
Scott-Stevens, Paul ;
Hosking, Louise ;
Dewit, Odile ;
Richardson, Jill C. ;
Chen, Chao .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 75 (01) :197-207
[6]   TELOMERE SHORTENING IS ASSOCIATED WITH CELL-DIVISION IN-VITRO AND IN-VIVO [J].
ALLSOPP, RC ;
CHANG, E ;
KASHEFIAAZAM, M ;
ROGAEV, EI ;
PIATYSZEK, MA ;
SHAY, JW ;
HARLEY, CB .
EXPERIMENTAL CELL RESEARCH, 1995, 220 (01) :194-200
[7]   A novel mechanism of action of tetracyclines: Effects on nitric oxide synthases [J].
Amin, AR ;
Attur, MG ;
Thakker, GD ;
Patel, PD ;
Vyas, PR ;
Patel, RN ;
Patel, IR ;
Abramson, SB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :14014-14019
[8]   CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation [J].
Auffray, Cedric ;
Fogg, Darin K. ;
Narni-Mancinelli, Emilie ;
Senechal, Brigitte ;
Trouillet, Celine ;
Saederup, Noah ;
Leemput, Julia ;
Bigot, Karine ;
Campisi, Laura ;
Abitbol, Marc ;
Molina, Thierry ;
Charo, Israel ;
Hume, David A. ;
Cumano, Ana ;
Lauvau, Gregoire ;
Geissmann, Frederic .
JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (03) :595-606
[9]   Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease [J].
Bard, F ;
Cannon, C ;
Barbour, R ;
Burke, RL ;
Games, D ;
Grajeda, H ;
Guido, T ;
Hu, K ;
Huang, JP ;
Johnson-Wood, K ;
Khan, K ;
Kholodenko, D ;
Lee, M ;
Lieberburg, I ;
Motter, R ;
Nguyen, M ;
Soriano, F ;
Vasquez, N ;
Weiss, K ;
Welch, B ;
Seubert, P ;
Schenk, D ;
Yednock, T .
NATURE MEDICINE, 2000, 6 (08) :916-919
[10]   Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder [J].
Barden, Nicholas ;
Harvey, Mario ;
Gagne, Bernard ;
Shink, Eric ;
Tremblay, Monique ;
Raymond, Catherine ;
Labbe, Michel ;
Villeneuve, Andre ;
Rochette, Denis ;
Bordeleau, Lise ;
Stadler, Herbert ;
Holsboer, Florian ;
Mueller-Myhsok, Bertram .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2006, 141B (04) :374-382