Microglia and Alzheimer's disease pathogenesis.

Abstract:

:The most visible and, until very recently, the only hypothesis regarding the involvement of microglial cells in Alzheimer's disease (AD) pathogenesis is centered around the notion that activated microglia are neurotoxin-producing immune effector cells actively involved in causing the neurodegeneration that is the cause for AD dementia. The concept of detrimental neuroinflammation has gained a strong foothold in the AD arena and is being expanded to other neurodegenerative diseases. This review takes a comprehensive and critical look at the overall evidence supporting the neuroinflammation hypothesis and points out some weaknesses. The current work also reviews evidence for an alternative theory, the microglial dysfunction hypothesis, which, although eliminating some of the shortcomings, does not necessarily negate the amyloid/neuroinflammation theory. The microglial dysfunction theory offers a different perspective on the identity of activated microglia and their role in AD pathogenesis taking into account the most recent insights gained from studying basic microglial biology.

journal_name

J Neurosci Res

authors

Streit WJ

doi

10.1002/jnr.20093

keywords:

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

1-8

issue

1

eissn

0360-4012

issn

1097-4547

journal_volume

77

pub_type

杂志文章,评审
  • Noninvasive early detection of brain edema in mice by near-infrared light scattering.

    abstract::Brain edema accounts for significant morbidity and mortality in many neurologic conditions such as head trauma, stroke, meningitis, and brain tumor. The water channel aquaporin-4 (AQP4) has been found to be an important determinant of brain water accumulation and clearance of excess brain water. We report the developm...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.20439

    authors: Thiagarajah JR,Papadopoulos MC,Verkman AS

    更新日期:2005-04-15 00:00:00

  • An analysis of peripheral neuronal survival factors present in muscle.

    abstract::Extracts of bovine heart, rat heart, and rat skeletal muscle were chromatographically separated and the fractions tested for their ability to maintain the survival of dissociated sympathetic, parasympathetic, and sensory neurones. Bovine heart contained at least five, rat heart at least six, and rat skeletal muscle at...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.490130303

    authors: Bonyhady RE,Hendry IA,Hill CE,Watters DJ

    更新日期:1985-01-01 00:00:00

  • Fucosyl-GM1 expression and amyloid-beta protein accumulation in PC12 cells.

    abstract::Gangliosides, sialic acid-containing glycosphingolipids, are ubiquitously expressed in all eukaryotic cells and are localized primarily in the plasma membrane. For a rat pheochromocytoma cell line, PC12, which has been used frequently as a model for investigating events leading to neuronal differentiation, it is gener...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.21031

    authors: Yanagisawa M,Ariga T,Yu RK

    更新日期:2006-11-01 00:00:00

  • Enzyme translocation in the course of regeneration of central primary afferent terminals in the substantia gelatinosa of the adult rodent spinal cord.

    abstract::Synaptic circuitry in the upper dorsal horn, disorganized due to transganglionic degenerative atrophy (evoked by blockade of retrograde axoplasmic transport in the related peripheral nerve), begins to be reestablished by a process of regenerative synaptoneogenesis as soon as retrograde transport is resumed. Central ax...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.490220110

    authors: Knyihár-Csillik E,Kreutzberg GW,Csillik B

    更新日期:1989-01-01 00:00:00

  • Cytokines, chemokines, and cytokine receptors in human microglia.

    abstract::Enriched populations of human microglial cells were isolated from mixed cell cultures prepared from embryonic human telencephalon tissues. Human microglial cells exhibited cell type-specific antigens for macrophage-microglia lineage cells including CD11b (Mac-1), CD68, B7-2 (CD86), HLA-ABC, HLA-DR and ricinus communis...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.10253

    authors: Lee YB,Nagai A,Kim SU

    更新日期:2002-07-01 00:00:00

  • Pharmacological characterization of the glutamate receptor in cultured astrocytes.

    abstract::Cultured astrocytes from neonatal rat cerebral hemispheres are depolarized by the excitatory neurotransmitter glutamate. In this study we have used selective agonists of different neuronal glutamate receptor subtypes, namely, the N-methyl-D-aspartate (NMDA), kainate, and quisqualate type, to characterize pharmacologic...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.490220307

    authors: Backus KH,Kettenmann H,Schachner M

    更新日期:1989-03-01 00:00:00

  • Calcium-activated neutral protease in the peripheral nerve, which requires microM order Ca2+, and its effect on the neurofilament triplet.

    abstract::There are two types of calcium-activated neutral protease (CANP), m-CANP and mu-CANP, following the nomenclature of Suzuki et al to show that each requires mM and microM Ca2+, respectively, for its activation. We found mu-CANP activity in a crude CANP fraction extracted from the peripheral nerve, which degraded the ne...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.490130306

    authors: Kamakura K,Ishiura S,Suzuki K,Sugita H,Toyokura Y

    更新日期:1985-01-01 00:00:00

  • Death of septal cholinergic neurons produced by chronic exposure to glutamate is prevented by the noncompetitive NMDA receptor/channel antagonist, MK-801: role of nerve growth factor and nitric oxide.

    abstract::To study the sequence of degenerative events possibly associated with cholinergic cell death in Alzheimer's disease, septal cholinergic neurons derived from rat embryonic brains were exposed to chronic excitotoxic stress by glutamate. Counts of choline acetyltransferase (ChAT)-immunopositive neurons and measurement of...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.490400608

    authors: Michel PP,Agid Y

    更新日期:1995-04-15 00:00:00

  • Rat Schwann cells express M1-M4 muscarinic receptor subtypes.

    abstract::The expression of different muscarinic receptor subtypes was analyzed in immature Schwann cells obtained from sciatic nerve of 2-day neonatal rats. By using RT-PCR analysis, we demonstrated the presence of M1, M2, M3, and M4 receptor subtypes in cultured Schwann cells, with M2 displaying the highest expression levels....

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.20874

    authors: Loreti S,Vilaró MT,Visentin S,Rees H,Levey AI,Tata AM

    更新日期:2006-07-01 00:00:00

  • Involvement of interleukin-1 in lipopolysaccaride-induced microglial activation and learning and memory deficits.

    abstract::We have developed an animal model of learning and memory impairment associated with activation of microglia in the mouse brain. Injection of lipopolysaccharide into the CA1 region of the mouse hippocampus resulted in an increased production of inflammatory cytokines, such as interleukin-1β. Immunostaining for interleu...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.22582

    authors: Tanaka S,Kondo H,Kanda K,Ashino T,Nakamachi T,Sekikawa K,Iwakura Y,Shioda S,Numazawa S,Yoshida T

    更新日期:2011-04-01 00:00:00

  • Mechanism of neuroprotection by donepezil pretreatment in rat cortical neurons chronically treated with donepezil.

    abstract::Previously, we showed that in rat cortical neurons, chronic donepezil treatment (10 microM, 4 days) up-regulates nicotinic receptors (nAChR) and makes neurons more sensitive to the neuroprotective effect of donepezil. Here we examined the mechanism of donepezil-induced neuroprotection in neurons chronically treated wi...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.21798

    authors: Takada-Takatori Y,Kume T,Ohgi Y,Izumi Y,Niidome T,Fujii T,Sugimoto H,Akaike A

    更新日期:2008-12-01 00:00:00

  • Alterations of central nervous system protein synthesis in response to spinal cord hemisection.

    abstract::This investigation explores the central nervous system protein-synthetic responses to hemisection of the spinal cord. Adult male rats hemisected at mid T2 were given intravenous injections of 14C-leucine at 0.7, 30, or 70 days postoperative. Four hours later the T1, T2, T3, and C6 segments of the spinal cord and right...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.490010107

    authors: Luttge WG,Mannis MJ,Bernstein JJ

    更新日期:1975-01-01 00:00:00

  • Cyclic AMP regulates substance P expression in developing and mature spinal sensory neurons.

    abstract::The tachykinin, substance P, has long been associated with transmission of noxious stimuli. However, relatively little is known about signal transduction pathways subserving peptidergic regulation in sensory neurons. To investigate whether cyclic AMP (cAMP) could be a potential second messenger subserving substance P ...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-4547(20000301)59:5<624::AID-JNR

    authors: Adler JE,Walker PD

    更新日期:2000-03-01 00:00:00

  • Distribution of neuronal intermediate filament proteins in the developing mouse olfactory system.

    abstract::The distribution of neuronal intermediate filament proteins in the developing mouse olfactory bulb and olfactory epithelium was characterized by immunocytochemical approach. Antibodies against alpha-internexin, neurofilament triplet proteins (NFTPs; NF-L, NF-M, and NF-H) and peripherin were used to determine their exp...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-4547(19981101)54:3<353::AID-JNR

    authors: Chien CL,Lee TH,Lu KS

    更新日期:1998-11-01 00:00:00

  • Uptake, release, and binding of taurine in degenerated rat retinas.

    abstract::High-affinity uptake, potassium-stimulated release and receptor binding of gamma-aminobutyric acid (GABA) and taurine were studied in retinas of rats treated with monosodium glutamate (MSG) or iodoacetate-malate (IAM). Such treatments produce a selective damage of the inner retinal layers (MSG) or of the photoreceptor...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.490080407

    authors: Salceda R,Pasantes-Morales H

    更新日期:1982-01-01 00:00:00

  • Acetylcholinesterase of Schistosoma mansoni: purification and characterization.

    abstract::Larval acetylcholinesterase (acetylcholine acetylhydrolase) EC 3.1.3.7 of the trematode Schistosoma mansoni was characterized and purified by affinity chromatography. The enzyme was solubilized from sonicated cercarial tissue and showed a Km value of 1.83 mM and a Vmax value of 102 U/mg protein. It was characterized a...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.490150413

    authors: Goldlust A,Arnon R,Silman I,Tarrab-Hazdai R

    更新日期:1986-01-01 00:00:00

  • Myelin-associated glycoprotein and its axonal receptors.

    abstract::Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin membrane wrap, directly apposed to the axon surface. Although it is not required for myelination, MAG enhances long-term axon-myelin stability, helps to structure nodes of Ranvier, and regulates the axon cytoskeleton. In addition to its role in ...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章,评审

    doi:10.1002/jnr.21992

    authors: Schnaar RL,Lopez PH

    更新日期:2009-11-15 00:00:00

  • Regulation of neural cell adhesion molecule polysialylation state by cell-cell contact and protein kinase C delta.

    abstract::Post-translational modification of neural cell adhesion molecule (NCAM) with alpha2,8-linked polysialic acid, which regulates homophilic adhesion and/or signal transduction events, is crucial to synaptic plasticity in the developing and adult brain. Evidence from in vitro models has implicated polysialylation in the r...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/1097-4547(20000915)61:6<636::AID-JNR7>3.0.

    authors: Gallagher HC,Odumeru OA,Regan CM

    更新日期:2000-09-15 00:00:00

  • Nerve growth factor-mediated increases in protein methylation occur predominantly at type I arginine methylation sites and involve protein arginine methyltransferase 1.

    abstract::Nerve growth factor (NGF)-specific signal transduction leads to changes in protein methylation during neuronal differentiation of PC12 cells (Cimato et al. [1997] J. Cell Biol. 138:1089-1103). In the present work, we demonstrate that, among NGF-regulated proteins, arginine methylation is more prevalent than carboxylme...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.10123

    authors: Cimato TR,Tang J,Xu Y,Guarnaccia C,Herschman HR,Pongor S,Aletta JM

    更新日期:2002-02-15 00:00:00

  • Involvement of TLCK-sensitive serine protease in colchicine-induced cell death of sympathetic neurons in culture.

    abstract::Superior cervical ganglion (SCG) cells from neonatal rats underwent apoptosis upon treatment with colchicine, a microtubule-disrupting agent. Western blotting and activity measurements showed that caspase-3 was indeed activated, but its peptide inhibitor (Ac-DEVD-CHO) neither suppressed nuclear fragmentation nor rescu...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.10008

    authors: Mitsui C,Sakai K,Ninomiya T,Koike T

    更新日期:2001-11-15 00:00:00

  • Involvement of matrix metalloproteinases-2 and -9 in the formation of a lacuna-like cerebral cavity.

    abstract::We used a modified pial vessel disruption (PVD) protocol with adult male Wistar rats to mimic small-vessel stroke in the cerebral cortex. Within 3 weeks, this lesion develops into a single lacuna-like cavity, which is fluid-filled and encapsulated by reactive astrocytes. Minocycline treatment that commences 1 hr after...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.23223

    authors: Cayabyab FS,Gowribai K,Walz W

    更新日期:2013-07-01 00:00:00

  • Inhibition of proteasome and Shaggy/Glycogen synthase kinase-3beta kinase prevents clearance of phosphorylated tau in Drosophila.

    abstract::Tauopathies, including Alzheimer's disease (AD), are a group of neurodegenerative disorders characterized by the presence of intraneuronal filamentous inclusions of abnormally phosphorylated tau protein. In AD brains, it has been shown that the level of abnormally phosphorylated tau is higher than in age-matched contr...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.21006

    authors: Blard O,Frébourg T,Campion D,Lecourtois M

    更新日期:2006-10-01 00:00:00

  • Ionic currents in normal and neurofibromatosis type 1-affected human Schwann cells: induction of tumor cell K current in normal Schwann cells by cyclic AMP.

    abstract::Comparisons were made of whole cell voltage clamp recordings from cultures of normal Schwann cells (SC) from three human subjects and from three neurofibrosarcoma cell lines. The whole cell K+ (K) currents of normal and tumor cells could be divided into three types based on voltage activation range, pharmacology, and ...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-4547(19981115)54:4<495::AID-JNR

    authors: Fieber LA

    更新日期:1998-11-15 00:00:00

  • Ceramide in rafts (detergent-insoluble fraction) mediates cell death in neurotumor cell lines.

    abstract::Detergent-resistant lipid microdomains (Rafts) were isolated from human oligodendroglioma (HOG), human neuroblastoma (LA-N-5), and immortalized dorsal root ganglion (F-11) cell lines by sucrose-density gradient ultracentrifugation and shown to be enriched in cholesterol, sphingomyelin, and ceramide. [(3)H]palmitate la...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.10549

    authors: Kilkus J,Goswami R,Testai FD,Dawson G

    更新日期:2003-04-01 00:00:00

  • Lovastatin treatment decreases mononuclear cell infiltration into the CNS of Lewis rats with experimental allergic encephalomyelitis.

    abstract::Mononuclear cell infiltration into the CNS and induction of inflammatory cytokines and iNOS in diseases like multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) have been implicated in subsequent disease pathogenesis and progression. We report that Lovastatin treatment blocks the clinical disease...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.1207

    authors: Stanislaus R,Singh AK,Singh I

    更新日期:2001-10-15 00:00:00

  • Altered genetic response to beta-adrenergic receptor activation in late passage C6 glioma cells.

    abstract::Previous studies have demonstrated variability in the phenotype of rat C6 glioma cells. In the present study, we compared morphology, growth rate, and beta-adrenergic regulation of gene expression in early (P39-47) and late (P55-90) passage C6 cells. Morphological changes were observed in five independently derived, l...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.490330213

    authors: Gubits RM,Yu H,Casey G,Munell F,Vitek MP

    更新日期:1992-10-01 00:00:00

  • Human immunodeficiency virus type 1 gp120 inhibits long-term potentiation via chemokine receptor CXCR4 in rat hippocampal slices.

    abstract::Human immunodeficiency virus type 1 (HIV-1) infection in its human host often results in progressive dementia and encephalopathy in adults and children, respectively. The mechanisms underlying virus-induced neurocognitive dysfunction are not fully understood. However, several studies strongly suggest that secretory vi...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.20745

    authors: Dong J,Xiong H

    更新日期:2006-02-15 00:00:00

  • Functional properties of neurons derived from fetal mouse neurospheres are compatible with those of neuronal precursors in vivo.

    abstract::Neural stem cells can be propagated in culture as neurospheres, yielding neurons and glial cells upon differentiation. Although the neurosphere model is widely used, the functional properties of the neurosphere-derived neurons have been only partially characterized, and it is unclear whether repeated passaging alters ...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.20835

    authors: Pagani F,Lauro C,Fucile S,Catalano M,Limatola C,Eusebi F,Grassi F

    更新日期:2006-06-01 00:00:00

  • Early-stage development of human induced pluripotent stem cell-derived neurons.

    abstract::Recent advances in human induced pluripotent stem cells (hiPSCs) offer new possibilities for biomedical research and clinical applications. Differentiated neurons from hiPSCs are expected to be useful for developing novel methods of treatment for various neurological diseases. However, the detailed process of function...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章

    doi:10.1002/jnr.23666

    authors: Ohara Y,Koganezawa N,Yamazaki H,Roppongi RT,Sato K,Sekino Y,Shirao T

    更新日期:2015-12-01 00:00:00

  • Embedded ensemble encoding hypothesis: The role of the "Prepared" cell.

    abstract::We here reconsider current theories of neural ensembles in the context of recent discoveries about neuronal dendritic physiology. The key physiological observation is that the dendritic plateau potential produces sustained depolarization of the cell body (amplitude 10-20 mV, duration 200-500 ms). Our central hypothesi...

    journal_title:Journal of neuroscience research

    pub_type: 杂志文章,评审

    doi:10.1002/jnr.24240

    authors: Antic SD,Hines M,Lytton WW

    更新日期:2018-09-01 00:00:00