?-synuclein is developmentally expressed in cultured rat brain oligodendrocytes

Richter‐Landsberg, Christiane; Gorath, Michaela; Trojanowski, John Q.; Lee, Virginia M.‐Y.

doi:10.1002/1097-4547(20001001)62:1<9::aid-jnr2>3.0.co;2-u

Cited by 131 publications

(68 citation statements)

References 23 publications

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“…Cultured astrocytes [27] and astrocytes in situ [28] express tau proteins. In addition, astrocytic and oligodendroglial fibrillary inclusions immunoreactive for tau proteins are a common pathological feature of several tauopathies, including progressive supranuclear palsy, multiple system atrophy, and some familial forms of frontotemporal dementias [29]. Our results suggest that human glial cells in situ express mainly the 0N tau mRNAs with three or four repeats.…”

Section: Discussionmentioning

confidence: 99%

Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's disease

et al. 2004

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In Alzheimer's disease (AD), selective expression of tau isoforms might underlie the susceptibility of different brain areas to develop neurofibrillary tangles and this pattern might change in the disease. In this study, we have analyzed in control subjects and in sporadic AD patients the pattern of expression of tau mRNA and tau proteins in areas unaffected (cerebellar cortex, white matter), moderately affected (occipital striate cortex, thalamus, caudate nucleus, and putamen) or strongly affected by neurofibrillary tangles (temporal and frontal associative cortex). After RT-PCR amplification, five products corresponding to the tau mRNAs containing exons 2 and 3, exon 2, without exons 2 or 3, with exon 10 and without exon 10 were identified. In control subjects, these five PCR products were present in all areas except in white matter, where transcripts with exons 2 or exons 2 and 3 were not identified. In AD patients, the same pattern of transcripts was observed in different areas, regardless of the presence of neurofibrillary lesions. After dephosphorylation of soluble tau proteins, the six tau isoforms were identified in the same areas by immunoblotting, including in the white matter, suggesting that most tau isoforms with exons 2 and 3 are transported along axons. The relative expression of 0N3R isoforms was higher in the temporal cortex than in the cerebellar cortex, both in control and AD subjects. The qualitative pattern of expression was identical in subjects with or without an APOE4 allele. Our results suggest that splicing regulation of the tau gene and the relative expression of tau isoforms are not significantly changed in sporadic cases of the disease, although differential expression of tau isoforms in temporal cortex might underlie this brain area susceptibility to neurofibrillary tangles formation.

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Section: Discussionmentioning

confidence: 99%

Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's disease

et al. 2004

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“…The unique architecture of the myelin sheath calls for dedicated oligodendroglial cytoskeletal machinery in the CNS (14,15). Tubulin, actin, and associated proteins have been well documented in oligodendrocytes, but the molecular mechanisms underlying the motility of the oligodendroglia͞myelin sheath remain poorly understood (16). The following evidence supports a role of JN in binding͞ regulating oligodendroglial cytoskeleton: (i) JN showed substantial colocalization in the myelin sheath with CNPase, a known cytoskeleton-related oligodendroglial protein (17)(18)(19).…”

Section: Jn: An Oligodendroglia Marker Of a Previously Unidentified Pmentioning

confidence: 99%

Juxtanodin: An oligodendroglial protein that promotes cellular arborization and 2′,3′-cyclic nucleotide-3′-phosphodiesterase trafficking

Zhang

Cao²,

Guo³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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In the process of screening cell-type-specific genes, we identified juxtanodin (JN), an oligodendroglial protein featuring a putative C-terminal actin-binding domain. At the cellular level, JN in the rat CNS colocalized with 2 ,3 -cyclic nucleotide-3 -phosphodiesterase (CNPase), a cytoskeleton-related oligodendroglial protein. In the myelin sheath, JN was found mainly in the abaxon and the lateral few terminal loops. Its apposition to the myelinated axon, through the latter, defined an axonal subregion, herewith termed juxtanode, at the Ranvier node-paranode junction. During forebrain ontogenesis, JN expression paralleled that of MBPs but lagged behind CNPase. Juxtanodin transfection promoted arborization of cultured OLN-93 cells and augmented endogenous CNPase expression and transport to the process arbors of cultured primary oligodendrocyte precursors. These results reveal JN as a cytoskeleton-related oligodendroglial protein that delineates the juxtanode and might serve oligodendrocyte motility, differentiation, or myelin-axon signaling. Functionally, JN may be involved in CNS myelination and͞or specialization of the node of Ranvier.myelin-axon interaction ͉ oligodendrocyte ͉ node of Ranvier ͉ cytoskeleton O ligodendroglia are highly specialized myelin-forming cells of the CNS. Adequate myelination serves to insulate and accelerate the propagation of action potentials. Abnormalities in myelin formation͞maintenance may underlie diverse neurological disorders, ranging from multiple sclerosis to schizophrenia (1, 2). Matched with highly specialized functions and unique architecture, various oligodendrocyte͞myelin-selective molecules, such as myelin basic protein (MBP), myelin-associated glycoprotein, and 2Ј,3Ј-cyclic nucleotide-3Ј-phosphodiesterase (CNPase), have been isolated and characterized (1, 3). It is likely that many more are yet to be revealed. The identification and characterization of such molecules will probably help elucidate molecular mechanisms of myelination and dys-or demyelinating diseases.The unique architecture of the myelin sheath entails specialized, yet elusive, cytoskeletal mechanisms of myelin-forming cells. Here, we report the molecular features, cellular expression, and functional roles of juxtanodin (JN), a previously unidentified cytoskeleton-related oligodendrocyte-specific protein. Materials and MethodsIdentification and Characterization of the mRNA. Cell-type-specific CNS genes were sought out by in situ hybridization histochemistry (ISH). Briefly, cDNA clones (n ϭ 1,500) from a rat brain cDNA library (Invitrogen) were sequenced and compared by BLAST searches against National Center for Biotechnology Information nucleotide and protein nonredundant databases (4). For the unannotated cDNA sequences (n ϭ 274), expression of the mRNAs in the CNS was mapped by ISH using digoxigeninlabeled riboprobes. A 3.6-kb cDNA clone with a predicted ORF encoding 282 amino acid residues was thereby identified, and the gene was subsequently named juxtanodin (JN). A search of EST databases revealed an...

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“…Thus, the in vivo encephalitogenic potential of the ␤-synuclein peptides alerted us to the unsuspected expression of ␤-synuclein in myelin. Interestingly, ␣-synuclein was reported to be expressed in oligodendrocytes (33). However, because axonal proteins may contaminate the myelin isolated on sucrose gradients, additional experiments that directly show the expression of ␤-synuclein in myelin are needed.…”

Section: ␤-Synuclein Is Present In Myelinmentioning

confidence: 99%

Autoimmune Encephalomyelitis and Uveitis Induced by T Cell Immunity to Self β-Synuclein

Mor

Quintana

Mimran

et al. 2003

The Journal of Immunology

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β-synuclein is a neuronal protein that accumulates in the plaques that characterize neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. It has been proposed that immunization to peptides of plaque-forming proteins might be used therapeutically to help dissociate pathogenic plaques in the brain. We now report that immunization of Lewis rats with a peptide from β-synuclein resulted in acute paralytic encephalomyelitis and uveitis. T cell lines and clones reactive to the peptide adoptively transferred the disease to naive rats. Immunoblotting revealed the presence of β-synuclein in heavy myelin, indicating that the expression of β-synuclein is not confined to neurons. These results add β-synuclein to the roster of encephalitogenic self Ags, point out the potential danger of therapeutic autoimmunization to β-synuclein, and alert us to the unsuspected possibility that autoimmunity to β-synuclein might play an inflammatory role in the pathogenesis of neurodegeneration.

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?-synuclein is developmentally expressed in cultured rat brain oligodendrocytes

Cited by 131 publications

References 23 publications

Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's disease

Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's disease

Juxtanodin: An oligodendroglial protein that promotes cellular arborization and 2′,3′-cyclic nucleotide-3′-phosphodiesterase trafficking

Autoimmune Encephalomyelitis and Uveitis Induced by T Cell Immunity to Self β-Synuclein

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