Welcome members and clients of OMMP PIF. Due to increased costs, our website has moved to this server, Thanks go to our Friend and colleague, Wired57, for making this possible. If you have any questions or concerns, please start a new topic in 
Thank you 
04-16-2012, 10:08 PM
Can marijuana help treat Alzheimer's disease?
General Reference (not clearly pro or con)
The National Institute on Aging stated in its Mar. 2006 booklet Understanding Alzheimer's Disease: "Alzheimer's disease is an illness of the brain. It causes large numbers of nerve cells in the brain to die. This affects your ability to remember things and think clearly. Doctors don't know what causes the disease. They do know that it usually begins after age 60 and nearly half of people age 85 and older may have Alzheimer's. However, it is not a normal part of aging...
There are medicines that can treat the symptoms of Alzheimer's. However, there is no cure. Some medicines keep your memory loss and other symptoms from getting worse for a time. These medicines work best if Alzheimer's disease is found early. Other medicines work to help you sleep better or feel less worried and depressed. These medicines don't directly treat the disease. They do help you feel more comfortable."
more
Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activation
Background
Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO), cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB<sub>2</sub>).
Methods
In this study, we investigated the effects of a cannabinoid agonist on CD40 exp<b></b>ression and function by cultured microglial cells activated by IFN- using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB<sub>2 </sub>small interfering RNA (siRNA) analyses. Furthermore, we examined if the stimulation of CB<sub>2 </sub>could modulate the capacity of microglial cells to phagocytise Ab<sub>142 </sub>peptide using a phagocytosis assay.
Results
We found that the selective stimulation of cannabinoid receptor CB<sub>2 </sub>by JWH-015 suppressed IFN--induced CD40 exp<b></b>ression. In addition, this CB<sub>2 </sub>agonist markedly inhibited IFN--induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-a and nitric oxide production induced either by IFN- or Ab peptide challenge in the presence of CD40 ligation. Finally, we showed that CB<sub>2 </sub>activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Ab<sub>142 </sub>peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB<sub>2 </sub>modulation in neurodegenerative diseases, particularly AD.
more
List of abbreviations
Ab : Amyloid-b peptide
CD40: CD40 receptor
CD40L: CD40 ligand
CNS: Central nervous system
HIV: Human immunodeficiency virus
IFN- : Interferon-gamma
JAK: Janus kinase
MHC II: Major histocompatibility complex II
STAT1: Signal transducer and activator of transcription 1
TNF-a : Tumor necrosis factor-alpha
Aloisi F, Penna G, Polazzi E, Minghetti L, Adorini L: CD40-CD154 interaction and IFN-gamma are required for IL-12 but not prostaglandin E2 secretion by microglia during antigen presentation to Th1 cells.
J Immunol 1999, 162:1384-1391. PubMed Abstract | Publisher Full Text OpenURL
Fischer HG, Reichmann G: Brain dendritic cells and macrophages/microglia in central nervous system inflammation.
J Immunol 2001, 166:2717-2726. PubMed Abstract | Publisher Full Text OpenURL
Aloisi F: Immune function of microglia.
Glia 2001, 36:165-179. PubMed Abstract | Publisher Full Text OpenURL
Tan J, Town T, Paris D, Placzek A, Parker T, Crawford F, Yu H, Humphrey J, Mullan M: Activation of microglial cells by the CD40 pathway: relevance to multiple sclerosis.
J Neuroimmunol 1999, 97:77-85. PubMed Abstract | Publisher Full Text OpenURL
Townsend KP, Town T, Mori T, Lue LF, Shytle D, Sanberg PR, Morgan D, Fernandez F, Flavell RA, Tan J: CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid beta-peptide.
Eur J Immunol 2005, 35:901-910. PubMed Abstract | Publisher Full Text OpenURL
Gerritse K, Laman JD, Noelle RJ, Aruffo A, Ledbetter JA, Boersma WJ, Claassen E: CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis.
Proc Natl Acad Sci U S A 1996, 93:2499-2504. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
Laman JD, Maassen CB, Schellekens MM, Visser L, Kap M, de Jong E, van Puijenbroek M, van Stipdonk MJ, van Meurs M, Schwarzler C, Gunthert U: Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces experimental autoimmune encephalomyelitis induced by a proteolipid protein peptide.
Mult Scler 1998, 4:147-153. PubMed Abstract | Publisher Full Text OpenURL
Boon L, Brok HP, Bauer J, Ortiz-Buijsse A, Schellekens MM, Ramdien-Murli S, Blezer E, van Meurs M, Ceuppens J, de Boer M, et al.: Prevention of experimental autoimmune encephalomyelitis in the common marmoset (Callithrix jacchus) using a chimeric antagonist monoclonal antibody against human CD40 is associated with altered B cell responses.
J Immunol 2001, 167:2942-2949. PubMed Abstract | Publisher Full Text OpenURL
Howard LM, Neville KL, Haynes LM, Dal Canto MC, Miller SD: CD154 blockade results in transient reduction in Theiler's murine encephalomyelitis virus-induced demyelinating disease.
J Virol 2003, 77:2247-2250. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
Tan J, Town T, Crawford F, Mori T, DelleDonne A, Crescentini R, Obregon D, Flavell RA, Mullan MJ: Role of CD40 ligand in amyloidosis in transgenic Alzheimer's mice.
Nat Neurosci 2002, 5:1288-1293. PubMed Abstract | Publisher Full Text OpenURL
Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ: Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease.
Int J Geriatr Psychiatry 1997, 12(9):913-9. PubMed Abstract | Publisher Full Text OpenURL
Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML: Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation.
J Neurosci 25(8):1904-13.
2005 Feb 23
PubMed Abstract | Publisher Full Text OpenURL
Wade DT, Makela P, Robson P, House H, Bateman C: Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.
Mult Scler 2004, 10(4):434-41. PubMed Abstract | Publisher Full Text OpenURL
Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A, UK MS Research Group: Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial.
Lancet 362(9395):1517-26.
2003 Nov 8
PubMed Abstract | Publisher Full Text OpenURL
Croxford JL, Miller SD: Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212.
J Clin Invest 2003, 111(8):1231-40. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
Town T, Tan J, Sansone N, Obregon D, Klein T, Mullan M: Characterization of murine immunoglobulin G antibodies against human amyloid-beta1-42.
Neurosci Lett 307(2):101-4.
2001 Jul 13
PubMed Abstract | Publisher Full Text OpenURL
Tan J, Town T, Mullan M: CD45 inhibits CD40L-induced microglial activation via negative regulation of the Src/p44/42 MAPK pathway.
J Biol Chem 2000, 275:37224-37231. PubMed Abstract | Publisher Full Text OpenURL
Tan J, Town T, Paris D, Mori T, Suo Z, Crawford F, Mattson MP, Flavell RA, Mullan M: Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation.
Science 1999, 286:2352-2355. PubMed Abstract | Publisher Full Text OpenURL
Tan J, Town T, Saxe M, Paris D, Wu Y, Mullan M: Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10.
J Immunol 1999, 163:6614-6621. PubMed Abstract | Publisher Full Text OpenURL
Kitamura Y, Nomura Y: Stress proteins and glial functions: possible therapeutic targets for neurodegenerative disorders.
Pharmacol Ther 2003, 97:35-53. PubMed Abstract | Publisher Full Text OpenURL
Webster SD, Galvan MD, Ferran E, Garzon-Rodriguez W, Glabe CG, Tenner AJ: Antibody-mediated phagocytosis of the amyloid beta-peptide in microglia is differentially modulated by C1q.
J Immunol 2001, 166:7496-7503. PubMed Abstract | Publisher Full Text OpenURL
Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, Silverstein SC, Husemann J: Adult mouse astrocytes degrade amyloid-beta in vitro and in situ.
Nat Med 2003, 9:453-457. PubMed Abstract | Publisher Full Text OpenURL
Nguyen VT, Walker WS, Benveniste EN: Post-transcriptional inhibition of CD40 gene exp<b></b>ression in microglia by transforming growth factor-beta.
Eur J Immunol 1998, 28:2537-2548. PubMed Abstract | Publisher Full Text OpenURL
Townsend KP, Shytle DR, Bai Y, San N, Zeng J, Freeman M, Mori T, Fernandez F, Morgan D, Sanberg P, Tan J: Lovastatin modulation of microglial activation via suppression of functional CD40 exp<b></b>ression.
J Neurosci Res 2004, 78:167-176. PubMed Abstract | Publisher Full Text OpenURL
Nguyen VT, Benveniste EN: IL-4-activated STAT-6 inhibits IFN-gamma-induced CD40 gene exp<b></b>ression in macrophages/microglia.
J Immunol 2000, 165:6235-6243. PubMed Abstract | Publisher Full Text OpenURL
Nguyen VT, Benveniste EN: Involvement of STAT-1 and ets family members in interferon-gamma induction of CD40 transcription in microglia/macrophages.
J Biol Chem 2000, 275:23674-23684. PubMed Abstract | Publisher Full Text OpenURL
Wei R, Jonakait GM: Neurotrophins and the anti-inflammatory agents interleukin-4 (IL-4), IL-10, IL-11 and transforming growth factor-beta1 (TGF-beta1) down-regulate T cell costimulatory molecules B7 and CD40 on cultured rat microglia.
J Neuroimmunol 1999, 95:8-18. PubMed Abstract | Publisher Full Text OpenURL
Delgado M: Inhibition of interferon (IFN) gamma-induced Jak-STAT1 activation in microglia by vasoactive intestinal peptide: inhibitory effect on CD40, IFN-induced protein-10, and inducible nitric-oxide synthase exp<b></b>ression.
J Biol Chem 2003, 278:27620-27629. PubMed Abstract | Publisher Full Text OpenURL
Kim WK, Ganea D, Jonakait GM: Inhibition of microglial CD40 exp<b></b>ression by pituitary adenylate cyclase-activating polypeptide is mediated by interleukin-10.
J Neuroimmunol 2002, 126:16-24. PubMed Abstract | Publisher Full Text OpenURL
Wallen-Ohman M, Larrick JW, Carlsson R, Borrebaeck CA: Ligation of MHC class I induces apoptosis in human pre-B cell lines, in promyelocytic cell lines and in CD40-stimulated mature B cells.
Int Immunol 1997, 9:599-606. PubMed Abstract | Publisher Full Text OpenURL
Chappel MS, Hough MR, Mittel A, Takei F, Kay R, Humphries RK: Cross-linking the murine heat-stable antigen induces apoptosis in B cell precursors and suppresses the anti-CD40-induced proliferation of mature resting B lymphocytes.
J Exp Med 1996, 184:1638-1649. PubMed Abstract | Publisher Full Text OpenURL
Aloisi F, De Simone R, Columba-Cabezas S, Penna G, Adorini L: Functional maturation of adult mouse resting microglia into an APC is promoted by granulocyte-macrophage colony-stimulating factor and interaction with Th1 cells.
J Immunol 2000, 164:1705-1712. PubMed Abstract | Publisher Full Text OpenURL
Magnus T, Chan A, Grauer O, Toyka KV, Gold R: Microglial phagocytosis of apoptotic inflammatory T cells leads to down-regulation of microglial immune activation.
J Immunol 2001, 167:5004-5010. PubMed Abstract | Publisher Full Text OpenURL
Chan A, Magnus T, Gold R: Phagocytosis of apoptotic inflammatory cells by microglia and modulation by different cytokines: mechanism for removal of apoptotic cells in the inflamed nervous system.
Glia 2001, 33:87-95. PubMed Abstract | Publisher Full Text OpenURL
Re F, Belyanskaya SL, Riese RJ, Cipriani B, Fischer FR, Granucci F, Ricciardi-Castagnoli P, Brosnan C, Stern LJ, Strominger JL, Santambrogio L: Granulocyte-macrophage colony-stimulating factor induces an exp<b></b>ression program in neonatal microglia that primes them for antigen presentation.
J Immunol 2002, 169:2264-2273. PubMed Abstract | Publisher Full Text OpenURL
Monsonego A, Imitola J, Zota V, Oida T, Weiner HL: Microglia-mediated nitric oxide cytotoxicity of T cells following amyloid beta-peptide presentation to Th1 cells.
J Immunol 2003, 171:2216-2224. PubMed Abstract | Publisher Full Text OpenURL
Monsonego A, Weiner HL: Immunotherapeutic approaches to Alzheimer's disease.
Science 2003, 302:834-838. PubMed Abstract | Publisher Full Text OpenURL
Berdyshev EV: Cannabinoid receptors and the regulation of immune response.
Chem Phys Lipids 2000, 108:169-190. PubMed Abstract | Publisher Full Text OpenURL
Wagner AH, Gebauer M, Guldenzoph B, Hecker M: 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent inhibition of CD40 exp<b></b>ression by atorvastatin in human endothelial cells.
Arterioscler Thromb Vasc Biol 2002, 22:1784-1789. PubMed Abstract | Publisher Full Text OpenURL
Schonbeck U, Gerdes N, Varo N, Reynolds RS, Horton DB, Bavendiek U, Robbie L, Ganz P, Kinlay S, Libby P: Oxidized low-density lipoprotein augments and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors limit CD40 and CD40L exp<b></b>ression in human vascular cells.
Circulation 2002, 106:2888-2893. PubMed Abstract | Publisher Full Text OpenURL
Mulhaupt F, Matter CM, Kwak BR, Pelli G, Veillard NR, Burger F, Graber P, Luscher TF, Mach F: Statins (HMG-CoA reductase inhibitors) reduce CD40 exp<b></b>ression in human vascular cells.
Cardiovasc Res 2003, 59:755-766. PubMed Abstract | Publisher Full Text OpenURL
Becher B, Durell BG, Miga AV, Hickey WF, Noelle RJ: The clinical course of experimental autoimmune encephalomyelitis and inflammation is controlled by the exp<b></b>ression of CD40 within the central nervous system.
J Exp Med 2001, 193:967-974. PubMed Abstract | Publisher Full Text OpenURL
Togo T, Akiyama H, Kondo H, Ikeda K, Kato M, Iseki E, Kosaka K: Exp<b></b>ression of CD40 in the brain of Alzheimer's disease and other neurological diseases.
Brain Res 2000, 885:117-121. PubMed Abstract | Publisher Full Text OpenURL
Calingasan NY, Erdely HA, Altar CA: Identification of CD40 ligand in Alzheimer's disease and in animal models of Alzheimer's disease and brain injury.
Neurobiol Aging 2002, 23:31-39. PubMed Abstract | Publisher Full Text OpenURL
Benveniste EN, Nguyen VT, Wesemann DR: Molecular regulation of CD40 gene exp<b></b>ression in macrophages and microglia.
Brain Behav Immun 2004, 18:7-12. PubMed Abstract | Publisher Full Text OpenURL
Yasukawa H, Sasaki A, Yoshimura A: Negative regulation of cytokine signaling pathways.
Annu Rev Immunol 2000, 18:143-164. PubMed Abstract | Publisher Full Text OpenURL
General Reference (not clearly pro or con)
The National Institute on Aging stated in its Mar. 2006 booklet Understanding Alzheimer's Disease: "Alzheimer's disease is an illness of the brain. It causes large numbers of nerve cells in the brain to die. This affects your ability to remember things and think clearly. Doctors don't know what causes the disease. They do know that it usually begins after age 60 and nearly half of people age 85 and older may have Alzheimer's. However, it is not a normal part of aging...
There are medicines that can treat the symptoms of Alzheimer's. However, there is no cure. Some medicines keep your memory loss and other symptoms from getting worse for a time. These medicines work best if Alzheimer's disease is found early. Other medicines work to help you sleep better or feel less worried and depressed. These medicines don't directly treat the disease. They do help you feel more comfortable."
more
Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activation
Background
Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO), cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB<sub>2</sub>).
Methods
In this study, we investigated the effects of a cannabinoid agonist on CD40 exp<b></b>ression and function by cultured microglial cells activated by IFN- using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB<sub>2 </sub>small interfering RNA (siRNA) analyses. Furthermore, we examined if the stimulation of CB<sub>2 </sub>could modulate the capacity of microglial cells to phagocytise Ab<sub>142 </sub>peptide using a phagocytosis assay.
Results
We found that the selective stimulation of cannabinoid receptor CB<sub>2 </sub>by JWH-015 suppressed IFN--induced CD40 exp<b></b>ression. In addition, this CB<sub>2 </sub>agonist markedly inhibited IFN--induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-a and nitric oxide production induced either by IFN- or Ab peptide challenge in the presence of CD40 ligation. Finally, we showed that CB<sub>2 </sub>activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Ab<sub>142 </sub>peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB<sub>2 </sub>modulation in neurodegenerative diseases, particularly AD.
more
List of abbreviations
Ab : Amyloid-b peptide
CD40: CD40 receptor
CD40L: CD40 ligand
CNS: Central nervous system
HIV: Human immunodeficiency virus
IFN- : Interferon-gamma
JAK: Janus kinase
MHC II: Major histocompatibility complex II
STAT1: Signal transducer and activator of transcription 1
TNF-a : Tumor necrosis factor-alpha
Aloisi F, Penna G, Polazzi E, Minghetti L, Adorini L: CD40-CD154 interaction and IFN-gamma are required for IL-12 but not prostaglandin E2 secretion by microglia during antigen presentation to Th1 cells.
J Immunol 1999, 162:1384-1391. PubMed Abstract | Publisher Full Text OpenURL
Fischer HG, Reichmann G: Brain dendritic cells and macrophages/microglia in central nervous system inflammation.
J Immunol 2001, 166:2717-2726. PubMed Abstract | Publisher Full Text OpenURL
Aloisi F: Immune function of microglia.
Glia 2001, 36:165-179. PubMed Abstract | Publisher Full Text OpenURL
Tan J, Town T, Paris D, Placzek A, Parker T, Crawford F, Yu H, Humphrey J, Mullan M: Activation of microglial cells by the CD40 pathway: relevance to multiple sclerosis.
J Neuroimmunol 1999, 97:77-85. PubMed Abstract | Publisher Full Text OpenURL
Townsend KP, Town T, Mori T, Lue LF, Shytle D, Sanberg PR, Morgan D, Fernandez F, Flavell RA, Tan J: CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid beta-peptide.
Eur J Immunol 2005, 35:901-910. PubMed Abstract | Publisher Full Text OpenURL
Gerritse K, Laman JD, Noelle RJ, Aruffo A, Ledbetter JA, Boersma WJ, Claassen E: CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis.
Proc Natl Acad Sci U S A 1996, 93:2499-2504. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
Laman JD, Maassen CB, Schellekens MM, Visser L, Kap M, de Jong E, van Puijenbroek M, van Stipdonk MJ, van Meurs M, Schwarzler C, Gunthert U: Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces experimental autoimmune encephalomyelitis induced by a proteolipid protein peptide.
Mult Scler 1998, 4:147-153. PubMed Abstract | Publisher Full Text OpenURL
Boon L, Brok HP, Bauer J, Ortiz-Buijsse A, Schellekens MM, Ramdien-Murli S, Blezer E, van Meurs M, Ceuppens J, de Boer M, et al.: Prevention of experimental autoimmune encephalomyelitis in the common marmoset (Callithrix jacchus) using a chimeric antagonist monoclonal antibody against human CD40 is associated with altered B cell responses.
J Immunol 2001, 167:2942-2949. PubMed Abstract | Publisher Full Text OpenURL
Howard LM, Neville KL, Haynes LM, Dal Canto MC, Miller SD: CD154 blockade results in transient reduction in Theiler's murine encephalomyelitis virus-induced demyelinating disease.
J Virol 2003, 77:2247-2250. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
Tan J, Town T, Crawford F, Mori T, DelleDonne A, Crescentini R, Obregon D, Flavell RA, Mullan MJ: Role of CD40 ligand in amyloidosis in transgenic Alzheimer's mice.
Nat Neurosci 2002, 5:1288-1293. PubMed Abstract | Publisher Full Text OpenURL
Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ: Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease.
Int J Geriatr Psychiatry 1997, 12(9):913-9. PubMed Abstract | Publisher Full Text OpenURL
Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML: Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation.
J Neurosci 25(8):1904-13.
2005 Feb 23
PubMed Abstract | Publisher Full Text OpenURL
Wade DT, Makela P, Robson P, House H, Bateman C: Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.
Mult Scler 2004, 10(4):434-41. PubMed Abstract | Publisher Full Text OpenURL
Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A, UK MS Research Group: Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial.
Lancet 362(9395):1517-26.
2003 Nov 8
PubMed Abstract | Publisher Full Text OpenURL
Croxford JL, Miller SD: Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212.
J Clin Invest 2003, 111(8):1231-40. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
Town T, Tan J, Sansone N, Obregon D, Klein T, Mullan M: Characterization of murine immunoglobulin G antibodies against human amyloid-beta1-42.
Neurosci Lett 307(2):101-4.
2001 Jul 13
PubMed Abstract | Publisher Full Text OpenURL
Tan J, Town T, Mullan M: CD45 inhibits CD40L-induced microglial activation via negative regulation of the Src/p44/42 MAPK pathway.
J Biol Chem 2000, 275:37224-37231. PubMed Abstract | Publisher Full Text OpenURL
Tan J, Town T, Paris D, Mori T, Suo Z, Crawford F, Mattson MP, Flavell RA, Mullan M: Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation.
Science 1999, 286:2352-2355. PubMed Abstract | Publisher Full Text OpenURL
Tan J, Town T, Saxe M, Paris D, Wu Y, Mullan M: Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10.
J Immunol 1999, 163:6614-6621. PubMed Abstract | Publisher Full Text OpenURL
Kitamura Y, Nomura Y: Stress proteins and glial functions: possible therapeutic targets for neurodegenerative disorders.
Pharmacol Ther 2003, 97:35-53. PubMed Abstract | Publisher Full Text OpenURL
Webster SD, Galvan MD, Ferran E, Garzon-Rodriguez W, Glabe CG, Tenner AJ: Antibody-mediated phagocytosis of the amyloid beta-peptide in microglia is differentially modulated by C1q.
J Immunol 2001, 166:7496-7503. PubMed Abstract | Publisher Full Text OpenURL
Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, Silverstein SC, Husemann J: Adult mouse astrocytes degrade amyloid-beta in vitro and in situ.
Nat Med 2003, 9:453-457. PubMed Abstract | Publisher Full Text OpenURL
Nguyen VT, Walker WS, Benveniste EN: Post-transcriptional inhibition of CD40 gene exp<b></b>ression in microglia by transforming growth factor-beta.
Eur J Immunol 1998, 28:2537-2548. PubMed Abstract | Publisher Full Text OpenURL
Townsend KP, Shytle DR, Bai Y, San N, Zeng J, Freeman M, Mori T, Fernandez F, Morgan D, Sanberg P, Tan J: Lovastatin modulation of microglial activation via suppression of functional CD40 exp<b></b>ression.
J Neurosci Res 2004, 78:167-176. PubMed Abstract | Publisher Full Text OpenURL
Nguyen VT, Benveniste EN: IL-4-activated STAT-6 inhibits IFN-gamma-induced CD40 gene exp<b></b>ression in macrophages/microglia.
J Immunol 2000, 165:6235-6243. PubMed Abstract | Publisher Full Text OpenURL
Nguyen VT, Benveniste EN: Involvement of STAT-1 and ets family members in interferon-gamma induction of CD40 transcription in microglia/macrophages.
J Biol Chem 2000, 275:23674-23684. PubMed Abstract | Publisher Full Text OpenURL
Wei R, Jonakait GM: Neurotrophins and the anti-inflammatory agents interleukin-4 (IL-4), IL-10, IL-11 and transforming growth factor-beta1 (TGF-beta1) down-regulate T cell costimulatory molecules B7 and CD40 on cultured rat microglia.
J Neuroimmunol 1999, 95:8-18. PubMed Abstract | Publisher Full Text OpenURL
Delgado M: Inhibition of interferon (IFN) gamma-induced Jak-STAT1 activation in microglia by vasoactive intestinal peptide: inhibitory effect on CD40, IFN-induced protein-10, and inducible nitric-oxide synthase exp<b></b>ression.
J Biol Chem 2003, 278:27620-27629. PubMed Abstract | Publisher Full Text OpenURL
Kim WK, Ganea D, Jonakait GM: Inhibition of microglial CD40 exp<b></b>ression by pituitary adenylate cyclase-activating polypeptide is mediated by interleukin-10.
J Neuroimmunol 2002, 126:16-24. PubMed Abstract | Publisher Full Text OpenURL
Wallen-Ohman M, Larrick JW, Carlsson R, Borrebaeck CA: Ligation of MHC class I induces apoptosis in human pre-B cell lines, in promyelocytic cell lines and in CD40-stimulated mature B cells.
Int Immunol 1997, 9:599-606. PubMed Abstract | Publisher Full Text OpenURL
Chappel MS, Hough MR, Mittel A, Takei F, Kay R, Humphries RK: Cross-linking the murine heat-stable antigen induces apoptosis in B cell precursors and suppresses the anti-CD40-induced proliferation of mature resting B lymphocytes.
J Exp Med 1996, 184:1638-1649. PubMed Abstract | Publisher Full Text OpenURL
Aloisi F, De Simone R, Columba-Cabezas S, Penna G, Adorini L: Functional maturation of adult mouse resting microglia into an APC is promoted by granulocyte-macrophage colony-stimulating factor and interaction with Th1 cells.
J Immunol 2000, 164:1705-1712. PubMed Abstract | Publisher Full Text OpenURL
Magnus T, Chan A, Grauer O, Toyka KV, Gold R: Microglial phagocytosis of apoptotic inflammatory T cells leads to down-regulation of microglial immune activation.
J Immunol 2001, 167:5004-5010. PubMed Abstract | Publisher Full Text OpenURL
Chan A, Magnus T, Gold R: Phagocytosis of apoptotic inflammatory cells by microglia and modulation by different cytokines: mechanism for removal of apoptotic cells in the inflamed nervous system.
Glia 2001, 33:87-95. PubMed Abstract | Publisher Full Text OpenURL
Re F, Belyanskaya SL, Riese RJ, Cipriani B, Fischer FR, Granucci F, Ricciardi-Castagnoli P, Brosnan C, Stern LJ, Strominger JL, Santambrogio L: Granulocyte-macrophage colony-stimulating factor induces an exp<b></b>ression program in neonatal microglia that primes them for antigen presentation.
J Immunol 2002, 169:2264-2273. PubMed Abstract | Publisher Full Text OpenURL
Monsonego A, Imitola J, Zota V, Oida T, Weiner HL: Microglia-mediated nitric oxide cytotoxicity of T cells following amyloid beta-peptide presentation to Th1 cells.
J Immunol 2003, 171:2216-2224. PubMed Abstract | Publisher Full Text OpenURL
Monsonego A, Weiner HL: Immunotherapeutic approaches to Alzheimer's disease.
Science 2003, 302:834-838. PubMed Abstract | Publisher Full Text OpenURL
Berdyshev EV: Cannabinoid receptors and the regulation of immune response.
Chem Phys Lipids 2000, 108:169-190. PubMed Abstract | Publisher Full Text OpenURL
Wagner AH, Gebauer M, Guldenzoph B, Hecker M: 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent inhibition of CD40 exp<b></b>ression by atorvastatin in human endothelial cells.
Arterioscler Thromb Vasc Biol 2002, 22:1784-1789. PubMed Abstract | Publisher Full Text OpenURL
Schonbeck U, Gerdes N, Varo N, Reynolds RS, Horton DB, Bavendiek U, Robbie L, Ganz P, Kinlay S, Libby P: Oxidized low-density lipoprotein augments and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors limit CD40 and CD40L exp<b></b>ression in human vascular cells.
Circulation 2002, 106:2888-2893. PubMed Abstract | Publisher Full Text OpenURL
Mulhaupt F, Matter CM, Kwak BR, Pelli G, Veillard NR, Burger F, Graber P, Luscher TF, Mach F: Statins (HMG-CoA reductase inhibitors) reduce CD40 exp<b></b>ression in human vascular cells.
Cardiovasc Res 2003, 59:755-766. PubMed Abstract | Publisher Full Text OpenURL
Becher B, Durell BG, Miga AV, Hickey WF, Noelle RJ: The clinical course of experimental autoimmune encephalomyelitis and inflammation is controlled by the exp<b></b>ression of CD40 within the central nervous system.
J Exp Med 2001, 193:967-974. PubMed Abstract | Publisher Full Text OpenURL
Togo T, Akiyama H, Kondo H, Ikeda K, Kato M, Iseki E, Kosaka K: Exp<b></b>ression of CD40 in the brain of Alzheimer's disease and other neurological diseases.
Brain Res 2000, 885:117-121. PubMed Abstract | Publisher Full Text OpenURL
Calingasan NY, Erdely HA, Altar CA: Identification of CD40 ligand in Alzheimer's disease and in animal models of Alzheimer's disease and brain injury.
Neurobiol Aging 2002, 23:31-39. PubMed Abstract | Publisher Full Text OpenURL
Benveniste EN, Nguyen VT, Wesemann DR: Molecular regulation of CD40 gene exp<b></b>ression in macrophages and microglia.
Brain Behav Immun 2004, 18:7-12. PubMed Abstract | Publisher Full Text OpenURL
Yasukawa H, Sasaki A, Yoshimura A: Negative regulation of cytokine signaling pathways.
Annu Rev Immunol 2000, 18:143-164. PubMed Abstract | Publisher Full Text OpenURL