Microglial Endocannabinoid Signalling in AD

Chronic inflammation in Alzheimer’s disease (AD) has been recently identified as a major contributor to disease pathogenesis. Once activated, microglial cells, which are brain-resident immune cells, exert several key actions, including phagocytosis, chemotaxis, and the release of pro- or anti-inflammatory mediators, which could have opposite effects on brain homeostasis, depending on the stage of disease and the particular phenotype of microglial cells. The endocannabinoids (eCBs) are pleiotropic bioactive lipids increasingly recognized for their essential roles in regulating microglial activity both under normal and AD-driven pathological conditions. Here, we review the current literature regarding the involvement of this signalling system in modulating microglial phenotypes and activity in the context of homeostasis and AD-related neurodegeneration.

[1]  Yafu Yin,et al.  Microglia Polarization From M1 to M2 in Neurodegenerative Diseases , 2022, Frontiers in Aging Neuroscience.

[2]  E. Denovan‐Wright,et al.  The Dynamic Role of Microglia and the Endocannabinoid System in Neuroinflammation , 2022, Frontiers in Pharmacology.

[3]  Hongzhuan Chen,et al.  TRPV1-Mediated Microglial Autophagy Attenuates Alzheimer’s Disease-Associated Pathology and Cognitive Decline , 2022, Frontiers in Pharmacology.

[4]  B. Peng,et al.  TRPV1 channel mediates NLRP3 inflammasome-dependent neuroinflammation in microglia , 2021, Cell Death & Disease.

[5]  Chu Chen,et al.  Endocannabinoid Metabolism and Traumatic Brain Injury , 2021, Cells.

[6]  M. Tremblay,et al.  Microglial Cannabinoid Type 1 Receptor Regulates Brain Inflammation in a Sex-Specific Manner. , 2021, Cannabis and cannabinoid research.

[7]  B. Cravatt,et al.  Potentiation of amyloid beta phagocytosis and amelioration of synaptic dysfunction upon FAAH deletion in a mouse model of Alzheimer's disease , 2021, Journal of neuroinflammation.

[8]  B. Xiao,et al.  Microglial Phenotypic Transition: Signaling Pathways and Influencing Modulators Involved in Regulation in Central Nervous System Diseases , 2021, Frontiers in Cellular Neuroscience.

[9]  T. Bisogno,et al.  Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization , 2021, International journal of molecular sciences.

[10]  Wei Zhou,et al.  TRPV1 sustains microglial metabolic reprogramming in Alzheimer's disease , 2021, EMBO reports.

[11]  V. Chiurchiù,et al.  Specialized Pro-resolving Lipid Mediators and Glial Cells: Emerging Candidates for Brain Homeostasis and Repair , 2021, Frontiers in Cellular Neuroscience.

[12]  Samuel S. Duffy,et al.  The cannabinoid system and microglia in health and disease , 2021, Neuropharmacology.

[13]  S. Haj-Dahmane,et al.  Mechanisms of endocannabinoid transport in the brain , 2021, British journal of pharmacology.

[14]  D. Mari,et al.  Anti-Inflammatory Effects of Fatty Acid Amide Hydrolase Inhibition in Monocytes/Macrophages from Alzheimer’s Disease Patients , 2021, Biomolecules.

[15]  E. Brennan,et al.  Recent advances in the design and development of formyl peptide receptor 2 (FPR2/ALX) agonists as pro-resolving agents with diverse therapeutic potential. , 2021, European journal of medicinal chemistry.

[16]  P. Edison,et al.  Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? , 2020, Nature Reviews Neurology.

[17]  M. Hinescu,et al.  CD36 in Alzheimer’s Disease: An Overview of Molecular Mechanisms and Therapeutic Targeting , 2020, Neuroscience.

[18]  K. Kuter,et al.  Overview of General and Discriminating Markers of Differential Microglia Phenotypes , 2020, Frontiers in Cellular Neuroscience.

[19]  M. Maccarrone,et al.  Bioactive lipids, inflammation and chronic diseases. , 2020, Advanced drug delivery reviews.

[20]  Yi-Hui Deng,et al.  Modulators of microglia activation and polarization in ischemic stroke , 2020, Molecular medicine reports.

[21]  Yumin Zhang,et al.  Endocannabinoid Modulation of Microglial Phenotypes in Neuropathology , 2020, Frontiers in Neurology.

[22]  T. Bisogno,et al.  Cannabinoids and the expanded endocannabinoid system in neurological disorders , 2019, Nature Reviews Neurology.

[23]  Kei Yamamoto,et al.  Intracellular Ca2+-dependent formation of N-acyl-phosphatidylethanolamines by human cytosolic phospholipase A2ε. , 2019, Biochimica et biophysica acta. Molecular and cell biology of lipids.

[24]  L. Buée,et al.  NLRP3 inflammasome activation drives tau pathology , 2019, Nature.

[25]  Jun Chen,et al.  STAT6/Arg1 promotes microglia/macrophage efferocytosis and inflammation resolution in stroke mice. , 2019, JCI insight.

[26]  K. Saijo,et al.  The Endocannabinoid System as a Window Into Microglial Biology and Its Relationship to Autism , 2019, Front. Cell. Neurosci..

[27]  Chao Li,et al.  CB2 Cannabinoid receptor agonist ameliorates novel object recognition but not spatial memory in transgenic APP/PS1 mice , 2019, Neuroscience Letters.

[28]  T. Bisogno,et al.  Targeted Lipidomics Investigation of N ‐acylethanolamines in a Transgenic Mouse Model of AD: A Longitudinal Study , 2019, European Journal of Lipid Science and Technology.

[29]  Yumin Zhang,et al.  Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells , 2019, Cells.

[30]  D. Friedman,et al.  Safety, efficacy, and mechanisms of action of cannabinoids in neurological disorders , 2019, The Lancet Neurology.

[31]  Í. Azcoitia,et al.  The endocannabinoid 2-AG enhances spontaneous remyelination by targeting microglia , 2019, Brain, Behavior, and Immunity.

[32]  D. Brooks,et al.  Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume , 2019, Neurology.

[33]  S. Warrier,et al.  Microglial inflammation and phagocytosis in Alzheimer's disease: Potential therapeutic targets , 2019, British journal of pharmacology.

[34]  B. Cravatt,et al.  Role of interleukin 1‐beta in the inflammatory response in a fatty acid amide hydrolase‐knockout mouse model of Alzheimer’s disease , 2018, Biochemical pharmacology.

[35]  F. Pavón,et al.  Pharmacological blockade of fatty acid amide hydrolase (FAAH) by URB597 improves memory and changes the phenotype of hippocampal microglia despite ethanol exposure , 2018, Biochemical pharmacology.

[36]  M. Colonna,et al.  The identity and function of microglia in neurodegeneration , 2018, Nature Immunology.

[37]  M. Heneka,et al.  Cannabinoid 1 Receptor Signaling on Hippocampal GABAergic Neurons Influences Microglial Activity , 2018, Front. Mol. Neurosci..

[38]  Taotao Lao,et al.  Roles of Microglial and Monocyte Chemokines and Their Receptors in Regulating Alzheimer's Disease-Associated Amyloid-β and Tau Pathologies , 2018, Front. Neurol..

[39]  C. Steinhäuser,et al.  Plaque‐dependent morphological and electrophysiological heterogeneity of microglia in an Alzheimer's disease mouse model , 2018, Glia.

[40]  A. Zimmer,et al.  Cannabinoid Receptor 2-Deficiency Ameliorates Disease Symptoms in a Mouse Model with Alzheimer's Disease-Like Pathology. , 2018, Journal of Alzheimer's disease : JAD.

[41]  M. T. Grande,et al.  Cannabinoid CB2 receptors in the mouse brain: relevance for Alzheimer’s disease , 2018, Journal of neuroinflammation.

[42]  J. Gan,et al.  The inhibition of CB1 receptor accelerates the onset and development of EAE possibly by regulating microglia/macrophages polarization , 2018, Journal of Neuroimmunology.

[43]  D. Mango,et al.  Early alteration of distribution and activity of hippocampal type‐1 cannabinoid receptor in Alzheimer's disease‐like mice overexpressing the human mutant amyloid precursor protein , 2018, Pharmacological research.

[44]  Alzheimer’s Association 2018 Alzheimer's disease facts and figures , 2018, Alzheimer's & Dementia.

[45]  Valerio Chiurchiù,et al.  Bioactive Lipids and Chronic Inflammation: Managing the Fire Within , 2018, Front. Immunol..

[46]  Hui Zheng,et al.  Practical considerations for choosing a mouse model of Alzheimer’s disease , 2017, Molecular Neurodegeneration.

[47]  B. Barres,et al.  Microglia and macrophages in brain homeostasis and disease , 2017, Nature Reviews Immunology.

[48]  C. Serhan,et al.  New pro-resolving n-3 mediators bridge resolution of infectious inflammation to tissue regeneration. , 2017, Molecular aspects of medicine.

[49]  D. Piomelli,et al.  TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice , 2017, Nature Communications.

[50]  M. Colonna,et al.  Microglia Function in the Central Nervous System During Health and Neurodegeneration. , 2017, Annual review of immunology.

[51]  M. Glass,et al.  Cannabinoid CB1 and CB2 Receptor Signaling and Bias , 2017, Cannabis and cannabinoid research.

[52]  M. Heneka,et al.  Danger‐associated molecular patterns in Alzheimer’s disease , 2017, Journal of leukocyte biology.

[53]  M. F. Troncoso,et al.  Galectin-1 circumvents lysolecithin-induced demyelination through the modulation of microglial polarization/phagocytosis and oligodendroglial differentiation , 2016, Neurobiology of Disease.

[54]  F. Maxfield,et al.  The endocytic pathway in microglia during health, aging and Alzheimer’s disease , 2016, Ageing Research Reviews.

[55]  M. A. Pozo,et al.  Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer's disease , 2016, Neuropharmacology.

[56]  L. Mestre,et al.  Microglia activation states and cannabinoid system: Therapeutic implications. , 2016, Pharmacology & therapeutics.

[57]  M. Doverskog,et al.  Acceleration of Amyloidosis by Inflammation in the Amyloid-Beta Marmoset Monkey Model of Alzheimer’s Disease , 2016, Journal of Alzheimer's disease : JAD.

[58]  T. Bisogno,et al.  Type-2 cannabinoid receptors in neurodegeneration. , 2016, Pharmacological research.

[59]  K. Rhodes,et al.  The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease , 2016, Nature.

[60]  F. LaFerla,et al.  Activity of muscarinic, galanin and cannabinoid receptors in the prodromal and advanced stages in the triple transgenic mice model of Alzheimer’s disease , 2016, Neuroscience.

[61]  R. Ransohoff A polarizing question: do M1 and M2 microglia exist? , 2016, Nature Neuroscience.

[62]  C. Limatola,et al.  Dark microglia: A new phenotype predominantly associated with pathological states , 2016, Glia.

[63]  C. McPherson,et al.  Microglial M1/M2 polarization and metabolic states , 2016, British journal of pharmacology.

[64]  J. Fernández-Ruiz,et al.  Potential of the cannabinoid CB2 receptor as a pharmacological target against inflammation in Parkinson's disease , 2016, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[65]  E. Mandelkow,et al.  Tau in physiology and pathology , 2015, Nature Reviews Neuroscience.

[66]  R. Maldonado,et al.  The endocannabinoid system in guarding against fear, anxiety and stress , 2015, Nature Reviews Neuroscience.

[67]  B. Cravatt,et al.  Endocannabinoid regulation of amyloid-induced neuroinflammation , 2015, Neurobiology of Aging.

[68]  O. Albayram,et al.  Enhanced microglial activity in FAAH(-/-) animals. , 2015, Life sciences.

[69]  Ainoa Rueda-Zubiaurre,et al.  Endocannabinoids drive the acquisition of an alternative phenotype in microglia , 2015, Brain, Behavior, and Immunity.

[70]  D. Otte,et al.  Expression Analysis of CB2-GFP BAC Transgenic Mice , 2015, PloS one.

[71]  N. Derugin,et al.  Lack of the scavenger receptor CD36 alters microglial phenotypes after neonatal stroke , 2015, Journal of neurochemistry.

[72]  L. Lue,et al.  Immune phenotypes of microglia in human neurodegenerative disease: challenges to detecting microglial polarization in human brains , 2015, Alzheimer's Research & Therapy.

[73]  R. Franco,et al.  Alternatively activated microglia and macrophages in the central nervous system , 2015, Progress in Neurobiology.

[74]  T. Nakagawa,et al.  Activation of mitochondrial transient receptor potential vanilloid 1 channel contributes to microglial migration , 2015, Glia.

[75]  Burkhard Becher,et al.  Immune attack: the role of inflammation in Alzheimer disease , 2015, Nature Reviews Neuroscience.

[76]  B. Przewłocka,et al.  Anandamide, Acting via CB2 Receptors, Alleviates LPS-Induced Neuroinflammation in Rat Primary Microglial Cultures , 2015, Neural plasticity.

[77]  D. Holtzman,et al.  Three dimensions of the amyloid hypothesis: time, space and 'wingmen' , 2015, Nature Neuroscience.

[78]  J. Rinne,et al.  Monoacylglycerol lipase inhibitor JZL184 reduces neuroinflammatory response in APdE9 mice and in adult mouse glial cells , 2015, Journal of Neuroinflammation.

[79]  Peter K. Stys,et al.  Inefficient clearance of myelin debris by microglia impairs remyelinating processes , 2015, Journal of Experimental Medicine.

[80]  O. Garaschuk,et al.  Neuroinflammation in Alzheimer's disease , 2015, The Lancet Neurology.

[81]  L. Battistini,et al.  Endocannabinoid signalling in innate and adaptive immunity , 2015, Immunology.

[82]  L. Xiong,et al.  Activation of murine microglial N9 cells is attenuated through cannabinoid receptor CB2 signaling. , 2015, Biochemical and biophysical research communications.

[83]  A. Pérez-Samartín,et al.  Blockade of monoacylglycerol lipase inhibits oligodendrocyte excitotoxicity and prevents demyelination in vivo , 2015, Glia.

[84]  S. Pasquaré,et al.  Normal aging in rats and pathological aging in human Alzheimer’s disease decrease FAAH activity: Modulation by cannabinoid agonists , 2014, Experimental Gerontology.

[85]  K. Mackie,et al.  Programming of neural cells by (endo)cannabinoids: from physiological rules to emerging therapies , 2014, Nature Reviews Neuroscience.

[86]  M. O’Banion,et al.  Are “Resting” Microglia More “M2”? , 2014, Front. Immunol..

[87]  R. Franco,et al.  The monoacylglycerol lipase inhibitor JZL184 is neuroprotective and alters glial cell phenotype in the chronic MPTP mouse model , 2014, Neurobiology of Aging.

[88]  Mauro Maccarrone,et al.  Endocannabinoids, Related Compounds and Their Metabolic Routes , 2014, Molecules.

[89]  A. Cuello,et al.  Neuronal driven pre-plaque inflammation in a transgenic rat model of Alzheimer's disease , 2014, Neurobiology of Aging.

[90]  F. Tchantchou,et al.  The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury , 2014, Neuropharmacology.

[91]  I. Bechmann,et al.  Microglial pathology , 2014, Acta neuropathologica communications.

[92]  Teng Jiang,et al.  Microglia in Alzheimer's Disease , 2014, BioMed research international.

[93]  P. Popovich,et al.  Pattern recognition receptors and central nervous system repair , 2014, Experimental Neurology.

[94]  M. O’Banion,et al.  Neuroinflammation and M2 microglia: the good, the bad, and the inflamed , 2014, Journal of Neuroinflammation.

[95]  S. Gordon,et al.  The M1 and M2 paradigm of macrophage activation: time for reassessment , 2014, F1000prime reports.

[96]  K. Mackie,et al.  Parsing the players: 2‐arachidonoylglycerol synthesis and degradation in the CNS , 2014, British journal of pharmacology.

[97]  T. Bisogno,et al.  The inhibition of 2-arachidonoyl-glycerol (2-AG) biosynthesis, rather than enhancing striatal damage, protects striatal neurons from malonate-induced death: a potential role of cyclooxygenase-2-dependent metabolism of 2-AG , 2013, Cell Death and Disease.

[98]  J. Delgado-García,et al.  Microglial activation underlies cerebellar deficits produced by repeated cannabis exposure. , 2013, The Journal of clinical investigation.

[99]  A. Finazzi Agro',et al.  Epigenetic mechanisms and endocannabinoid signalling , 2013, The FEBS Journal.

[100]  R. Franco,et al.  CB2 receptor and amyloid pathology in frontal cortex of Alzheimer's disease patients , 2013, Neurobiology of Aging.

[101]  W. Wong Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation , 2013, Front. Cell. Neurosci..

[102]  G. Feng,et al.  Monoacylglycerol lipase is a therapeutic target for Alzheimer's disease. , 2012, Cell reports.

[103]  K. Blennow,et al.  Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. , 2012, Archives of neurology.

[104]  B. Jin,et al.  Transient receptor potential vanilloid subtype 1 contributes to mesencephalic dopaminergic neuronal survival by inhibiting microglia-originated oxidative stress , 2012, Brain Research Bulletin.

[105]  B. Cravatt,et al.  DAGLβ Inhibition Perturbs a Lipid Network Involved in Macrophage Inflammatory Responses , 2012, Nature chemical biology.

[106]  J. Borrell,et al.  CD200‐CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation , 2012, Glia.

[107]  F. Moradi,et al.  WIN55212-2 attenuates amyloid-beta-induced neuroinflammation in rats through activation of cannabinoid receptors and PPAR-γ pathway , 2012, Neuropharmacology.

[108]  D. Nomura,et al.  A dysregulated endocannabinoid-eicosanoid network supports pathogenesis in a mouse model of Alzheimer's disease. , 2012, Cell reports.

[109]  M. Lynch,et al.  The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation , 2012, Journal of Neuroinflammation.

[110]  Alberto Mantovani,et al.  Orchestration of metabolism by macrophages. , 2012, Cell metabolism.

[111]  Sean R. Donohue,et al.  [125I]SD-7015 reveals fine modalities of CB1 cannabinoid receptor density in the prefrontal cortex during progression of Alzheimer’s disease , 2012, Neurochemistry International.

[112]  M. Delgado,et al.  Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice , 2012, Journal of Neuroinflammation.

[113]  M. Maccarrone,et al.  The endocannabinoid system: an overview , 2011, Front. Behav. Neurosci..

[114]  D. Nomura,et al.  Endocannabinoid Hydrolysis Generates Brain Prostaglandins That Promote Neuroinflammation , 2011, Science.

[115]  B. Strooper,et al.  The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics , 2011, Nature Reviews Drug Discovery.

[116]  Masahiko Watanabe,et al.  Molecular reorganization of endocannabinoid signalling in Alzheimer's disease. , 2011, Brain : a journal of neurology.

[117]  K. Manaye,et al.  Distribution patterns of cannabinoid CB1 receptors in the hippocampus of APPswe/PS1ΔE9 double transgenic mice , 2011, Brain Research.

[118]  T. Hortobágyi,et al.  WNT signaling in activated microglia is proinflammatory , 2011, Glia.

[119]  S. Nam,et al.  Inflammation and Alzheimer’s disease , 2010, Archives of pharmacal research.

[120]  N. Stella Cannabinoid and cannabinoid‐like receptors in microglia, astrocytes, and astrocytomas , 2010, Glia.

[121]  M. Glass,et al.  THEMED ISSUE: CANNABINOIDS REVIEW The endocannabinoid system as a target for the treatment of neurodegenerative disease , 2010 .

[122]  R. Pertwee Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. , 2010, Current medicinal chemistry.

[123]  M. Citron Alzheimer's disease: strategies for disease modification , 2010, Nature Reviews Drug Discovery.

[124]  A. Spagnolo,et al.  Anandamide enhances IL‐10 production in activated microglia by targeting CB2 receptors: Roles of ERK1/2, JNK, and NF‐κB , 2010, Glia.

[125]  N. Stella Endocannabinoid signaling in microglial cells , 2009, Neuropharmacology.

[126]  A. Kluge,et al.  Barriers to Organizational Learning: An Integration of Theory and Research , 2009 .

[127]  H. Braak,et al.  Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease , 2009, Acta Neuropathologica.

[128]  Z Walker,et al.  Microglial activation and amyloid deposition in mild cognitive impairment , 2009, Neurology.

[129]  Rebecca M. Sappington,et al.  Contribution of TRPV1 to microglia-derived IL-6 and NFkappaB translocation with elevated hydrostatic pressure. , 2008, Investigative ophthalmology & visual science.

[130]  B. Cravatt,et al.  A Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2‐Arachidonoylglycerol , 2007, Chemistry & biology.

[131]  J. Whitaker,et al.  Inhibition of microglial fatty acid amide hydrolase modulates LPS stimulated release of inflammatory mediators , 2007, FEBS letters.

[132]  E. Cudaback,et al.  Identification of a Novel Endocannabinoid-Hydrolyzing Enzyme Expressed by Microglial Cells , 2007, The Journal of Neuroscience.

[133]  E. Fama,et al.  Migration , 2007, Inward Looking.

[134]  D. S. Zahm,et al.  Lipopolysaccharide and cyclic AMP regulation of CB2 cannabinoid receptor levels in rat brain and mouse RAW 264.7 macrophages , 2006, Journal of Neuroimmunology.

[135]  Bill X. Huang,et al.  A biosynthetic pathway for anandamide , 2006, Proceedings of the National Academy of Sciences.

[136]  P. Anand,et al.  COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord , 2006, BMC neurology.

[137]  Yun Bai,et al.  Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation , 2005, Journal of Neuroinflammation.

[138]  Judit K. Makara,et al.  Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus , 2005, Nature Neuroscience.

[139]  T. Klein Cannabinoid-based drugs as anti-inflammatory therapeutics , 2005, Nature Reviews Immunology.

[140]  M. L. de Ceballos,et al.  Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation , 2005, The Journal of Neuroscience.

[141]  E. E. Bagley,et al.  Cellular actions of somatostatin on rat periaqueductal grey neurons in vitro , 2004, British journal of pharmacology.

[142]  W. Campbell,et al.  Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. , 2004, Molecular pharmacology.

[143]  Gareth Williams,et al.  Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain , 2003, The Journal of cell biology.

[144]  M. Maccarrone,et al.  The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis , 2003, Cell Death and Differentiation.

[145]  K. Mackie,et al.  Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration , 2003, The Journal of Neuroscience.

[146]  K. Waku,et al.  2-Arachidonoyl-sn-glycero-3-phosphate, an arachidonic acid-containing lysophosphatidic acid: occurrence and rapid enzymatic conversion to 2-arachidonoyl-sn-glycerol, a cannabinoid receptor ligand, in rat brain. , 2002, Archives of biochemistry and biophysics.

[147]  D. Piomelli,et al.  A second endogenous cannabinoid that modulates long-term potentiation , 1997, Nature.

[148]  Stephen P. Mayfield,et al.  Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides , 1996, Nature.

[149]  M. Herkenham,et al.  Cannabinoid receptor binding and messenger RNA expression in human brain: An in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer's brains , 1994, Neuroscience.

[150]  H. Higgs,et al.  Identification of a phosphatidic acid-preferring phospholipase A1 from bovine brain and testis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[151]  L. Horrocks,et al.  Neurochemical aspects of Alzheimer's disease: Involvement of membrane phospholipids , 1988, Metabolic Brain Disease.

[152]  R. Swerdlow,et al.  Effects of Microglial Cytokines on Alzheimer's Disease-Related Phenomena. , 2019, Journal of Alzheimer's disease : JAD.

[153]  Liangyu Zhang,et al.  Nrf2/ARE pathway inhibits ROS-induced NLRP3 inflammasome activation in BV2 cells after cerebral ischemia reperfusion , 2017, Inflammation Research.

[154]  I. Ferrer,et al.  1 CB 1 agonist ACEA protects neurons and reduces the cognitive impairment of AßPP / PS 1 mice , 2015 .

[155]  Ester Asoa,et al.  1 CB 2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in A PP / PS 1 mice , 2015 .

[156]  P. Davies,et al.  CB2 Receptor Deficiency Increases Amyloid Pathology and Alters Tau Processing in a Transgenic Mouse Model of Alzheimer’s Disease , 2013, Molecular Medicine.

[157]  Masahiko Watanabe,et al.  Endocannabinoid-mediated control of synaptic transmission. , 2009, Physiological reviews.

[158]  Sonja Zehetmayer,et al.  Gene expression as peripheral biomarkers for sporadic Alzheimer's disease. , 2009, Journal of Alzheimer's disease : JAD.

[159]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[160]  G. Cabral,et al.  Cannabinoid-mediated inhibition of inducible nitric oxide production by rat microglial cells: evidence for CB1 receptor participation. , 2001, Advances in experimental medicine and biology.