ライフサイエンスコーパス: myelin

1 tex, but not in animals that cannot form new myelin.

2 endrocytes maintaining excessive and ectopic myelin.

3 and myelin-associated glycoprotein (MAG) on myelin.

4 of a peripheral membrane protein from human myelin.

5 lipids that must be transported to form new myelin.

6 rocytes contact and wrap neuronal axons with myelin.

7 ished along axon segments previously lacking myelin.

8 rve, mechanosensitive axons are insulated by myelin, a multilamellar membrane formed by Schwann cells

9 ermore, developmental analysis revealed that myelin abnormalities were already observed during the on

10 yelination, and its absence leads to several myelin abnormalities.

11 Efficient clearance of myelin after injury by Schwann cells is important for ax

12 duced capacity of these cells to phagocytose myelin and apoptotic T cells.

13 We report exacerbated myelin and axon loss in middle-aged (8-10 months of age)

14 While work has focused on myelin and axon loss in MS, less is known about mechanis

15 y removing neuron-derived components such as myelin and cell debris.

16 neurite density and dispersion, free water, myelin and cell metabolism were assessed with Neurite Or

17 l patterns of gene expression, intracortical myelin and cortical thickness, as well as structural and

18 oles, particularly in phagocytosis of mature myelin and in generating the vast amounts of membrane pr

19 Changes in markers of surface morphology, myelin and iron concentration of the basal ganglia and t

20 sclerosis (MS) is the inexorable loss of CNS myelin and latterly neurons leading to permanent neurolo

21 instead ensures selective high expression of myelin and lipid biosynthesis genes and proper repressio

22 Myelin and lymphocyte protein (MAL) is a tetraspan integ

23 ate the important role for a myelin protein, myelin and lymphocyte protein (MAL), in the process of c

24 in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a mult

25 experiments indicated 4-AP stabilization of myelin and oligodendrocyte precursor cells associated wi

26 ated by the fate of cholesterol from damaged myelin and oligodendroglial sterol synthesis.

27 n, the metabolic axonal support functions of myelin and the proposed contribution of myelin to CNS pl

28 amples were stained for proteolipid protein (myelin) and scored for cortical lesion types I-IV (mixed

29 opment, function and pathology of peripheral myelin, and a straightforward, accurate and sensitive wo

30 , where it is essential for the stability of myelin, and at the apical membrane of epithelial cells,

31 to investigate B cell function in additional myelin antigen contexts.

32 and completely abrogates immune responses to myelin antigen in the spleen.

33 hermore, macrophages require GALC to degrade myelin, as Galc-deficient macrophages are transformed in

34 lacking YAP/TAZ, however, fail to upregulate myelin-associated genes and completely fail to remyelina

35 myelination, myelin basic protein (MBP) and myelin-associated glycoprotein (MAG) myelin proteins wer

36 n GD1a and GT1b gangliosides on the axon and myelin-associated glycoprotein (MAG) on myelin.

37 Among limitations on neural recovery are myelin-associated inhibitors functioning as ligands for

38 e explored the secretion and activity of the myelin-associated neurite outgrowth inhibitor Nogo-A and

39 al and biochemical analysis using markers of myelin, astrocytes, microglia, neurons, globoid cells, a

40 a heterogeneous set of molecules, including myelin, axonal cytoskeleton, and ion channel antigens, i

41 ing events of the functionally active 84-104 myelin basic protein (MBP(84-104)) fragment released aft

42 Myelin basic protein (MBP) and its interaction with lipi

43 Regarding postnatal myelination, myelin basic protein (MBP) and myelin-associated glycopr

44 ed that an MHC class I-restricted epitope of myelin basic protein (MBP) is presented in the CNS durin

45 e for mTOR in expression and localization of myelin basic protein (Mbp) mRNA and MBP protein to the c

46 illary acidic protein (GFAP, p = 0.0074) and myelin basic protein (MBP, p = 0.0039) after FUS sonicat

47 able to simultaneously bind the longer 21mer myelin basic protein A2RE.

48 ite matter injury, characterized by impaired myelin basic protein and neurofilament NF200, the reduce

49 MS2-3C8) that recognizes a self-peptide from myelin basic protein presented by the MHC class II molec

50 as well as GalC(+)/O1(+) premyelinating and myelin basic protein(+)/myelin oligodendrocyte glycoprot

51 l as expression and cellular localization of myelin basic protein.

52 resistance to chronic microglial activation, myelin breakdown, hippocampal neuronal loss, and behavio

53 t mutations in the PLP1 gene, and absence of myelin by MRI.

54 The remaining ultrashort T2 signal from myelin can be detected with an ultrashort echo time (UTE

55 Myelin can be restored by regenerating oligodendrocytes

56 between-species alignment, based on cortical myelin, can predict changes in connectivity patterns acr

57 phagocytose myelin debris but fail to clear myelin cholesterol, resulting in cholesteryl ester (CE)

58 tial for myelination but has a novel role in myelin clearance after injury.SIGNIFICANCE STATEMENT Our

59 Improved understanding of myelin clearance allows for the identification of pathwa

60 that are potentially accessible to increase myelin clearance and improve remyelination and recovery.

61 indicating a possible mechanism for impaired myelin clearance.

62 oles in removing excess cytoplasm to promote myelin compaction and development of oligodendrocytes, a

63 cantly improved HL, nerve fiber density, and myelin compaction.

64 , CnB(scko) mice have slower degeneration of myelin compared with WT mice.

65 logical features such as cortical thickness, myelin content, and gene expression that change along th

66 d/T2-weighted [T1w/T2w] ratio as a marker of myelin content, inflammation, and edema), and cerebral b

67 asures exhibit the highest correlations with myelin content.

68 es show that activity-dependent formation of myelin contributes to memory consolidation and recall, p

69 tivation prevented oligodendrocyte death and myelin damage in the EAE model.

70 how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regener

71 d by myeloid cells regulates phagocytosis of myelin debris and apoptotic cells that can accumulate an

72 TREM2-deficient microglia phagocytose myelin debris but fail to clear myelin cholesterol, resu

73 cessitates the clearance of cholesterol-rich myelin debris by microglia/macrophages and the switch fr

74 NF-alpha, which are essential for phagocytic myelin debris clearance and for oligodendrogenesis.

75 mmatory phagocytic signaling is required for myelin debris degradation, for inflammation resolution,

76 were not only impaired in the degradation of myelin debris, but also in initiating the generation of

77 ce of CnB in primary SCs delays clearance of myelin debris.

78 f unedited RNA, rescues both melanocytes and myelin defects in vitro, suggesting that ADAR1 safeguard

79 Here, we offer first evidence that a myelin degradation product induces mechanical hypersensi

80 estic ferret presented with an overall lower myelin density throughout the amygdaloid body than the b

81 Ventromedial prefrontal myelin density, indexed by magnetisation transfer, corre

82 disorders characterized by a primary lack of myelin deposition.

83 Myelin destruction is followed by resident glia activati

84 ain's endogenous capacity to restore damaged myelin deteriorates during the course of demyelinating d

85 increases in density, but the time course of myelin development across discrete song nuclei has not b

86 notransduction, cytoskeletal reorganization, myelin development and axon survival.

87 We examined myelin development in the brains of the zebra finch (Tae

88 ase Activated Receptor 1 (PAR1), accelerates myelin development.

89 oligodendrocyte maturation and expression of myelin differentiation markers.

90 tablishing a new pharmaceutical modality for myelin disorders.

91 alization methods for accurate prediction of myelin distribution over large brain regions.

92 , accurate and sensitive workflow to address myelin diversity in health and disease.

93 le biomarker that may be suitable to monitor myelin dynamics and evaluate treatments aiming at remyel

94 ges across all neuronal subtypes, or whether myelin dynamics vary between neuronal classes to enable

95 ty, and the evidence for oligodendrocyte and myelin dysfunction in neurodevelopmental disorders with

96 have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity t

97 se mice display tomacula formed by excessive myelin folding, a pathological hallmark of HNPP, as have

98 Rapid Estimation of Myelin for Diagnostic Imaging provides robust myelin qua

99 s, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging tech

100 Disorders that disrupt myelin formation during development or in adulthood, suc

101 strate that pharmacological induction of new myelin formation with clemastine fumarate improves remot

102 The generation of myelin-forming oligodendrocytes persists throughout life

103 Longitudinally, these myelin fractions correlated with follow-up physical disa

104 hole-brain and normal-appearing white matter myelin fractions, which correlated with baseline cogniti

105 eads to global depigmentation and absence of myelin from peripheral nerves, resulting from alteration

106 rmalities paralleled by defective peripheral myelin gene expression.

107 opy number variation of the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes

108 genes, collectively resulting in functional myelin generation.

109 accompanied by a reduction in expression of myelin genes and a delay in Schwann cell differentiation

110 cells (OPCs) rapidly increased expression of myelin genes and myelin proteins, suggesting a direct in

111 igger promyelinating signals that upregulate myelin genes.

112 cell transplantation into the CNS to restore myelin has been tested in animal models of severe forms

113 proaches to peripheral nerves and peripheral myelin have fallen behind evolving technical standards.

114 Myelin images are generated by subtracting the second ec

115 echo time sequence can generate whole-brain myelin images specifically with a clinical 3-T scanner.

116 Rapid myelin imaging correlated with myelin-related stains (pr

117 Myelin imaging is often hampered by long scanning times,

118 tion of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simulta

119 Rapid myelin imaging was applied using 3T MRI ex vivo in 3 mul

120 pose To develop patient-specific whole-brain myelin imaging with a three-dimensional double-echo slid

121 Here, we analyze the role of myelin in auditory information processing using paradigm

122 h, we identified a mutant with disruption to myelin in both the CNS and PNS caused by a mutation in a

123 signal suppression for volumetric imaging of myelin in the brain and showed excellent myelin signal c

124 of transplanted neural stem cells to restore myelin in the context of PLP overexpression.

125 direct ultrashort echo time (UTE) imaging of myelin in vivo because water contributes most of the sig

126 As the brain develops, myelin increases in density, but the time course of myel

127 hile sustained intracellular accumulation of myelin induced a lesion-promoting phenotype.

128 t mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and micr

129 Outcomes in two unique models of myelin injury and repair, that is lysolecithin or cupriz

130 te the adult brain in the cuprizone model of myelin injury and repair.

131 ion across two experimental murine models of myelin injury.

132 ctivation in phagocytes occurs rapidly after myelin injury.

133 x is also reduced, consistent with disrupted myelin integrity.

134 ivity-related solute homeostasis at the axon-myelin interface, and the integrity of myelinated axons.

135 swelling of the periaxonal space at the axon-myelin interface.

136 velopment, plasticity, and diseases in which myelin is affected.

137 S and PNS myelination.SIGNIFICANCE STATEMENT Myelin is critical for the normal function of the nervou

138 The interface between an axon and myelin is maintained by a number of biomolecular interac

139 mal GLUT1 expression in oligodendrocytes and myelin is needed to metabolically support axonal functio

140 measure is the most suitable for quantifying myelin is still ongoing.

141 r mice with fingolimod significantly rescued myelin levels compared with vehicle-treated animals and

142 twitcher mouse model) significantly rescues myelin levels.

143 d lipid headgroups stably anchored P2 on the myelin-like bilayer surface.

144 Here, cryo-EM of myelin-like proteolipid multilayers revealed an ordered

145 revious studies observed that changes in the myelin lipid composition lead to instabilities and enhan

146 ter group developed greater acute axonal and myelin loss attributed to elevated oxidative stress thro

147 inflammation-related tissue swelling and/or myelin loss in APOE-epsilon4.

148 Myelin loss limits neurological recovery and myelin rege

149 In EAE and in the cuprizone model, areas of myelin loss, which are likely to remyelinate, was associ

150 ted with decreased oxidative stress and axon/myelin loss.

151 , visualizing supramolecular assembly at the myelin major dense line.

152 he drastic drop in specific dopaminergic and myelin markers.

153 lular processes where it is necessary at the myelin membrane for axon wrapping.

154 N-Wasp activity is essential for myelin membrane wrapping by Schwann cells, but its role

155 evels as a prerequisite for synthesizing new myelin membranes.

156 ffectively compete and replace the defective myelin (n = 2 at each of four end points).

157 In this study, we demonstrate that myelin obtained post mortem from 8 out of 11 MS brain do

158 Sciatic nerves of such mice showed thinner myelin of large diameter axons and gross aberrations in

159 Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are

160 mpare clinical features, disease course, and myelin oligodendrocyte glycoprotein (MOG) antibody (Ab)

161 y (EAE) induced by immunization of mice with myelin oligodendrocyte glycoprotein (MOG)(35-55) Ig-like

162 he AhR agonist ITE and a T cell epitope from myelin oligodendrocyte glycoprotein (MOG)(35-55) induced

163 tein levels of proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG), the membrane

164 Ab-seropositive, 3 double-Ab-seronegative, 4 myelin oligodendrocyte glycoprotein (MOG)-Ab-seropositiv

165 argely confined to induction with either the myelin oligodendrocyte glycoprotein epitope MOG(35-55) o

166 Inducing EAE by immunization with a myelin oligodendrocyte glycoprotein peptide (MOG(35-55))

167 ) premyelinating and myelin basic protein(+)/myelin oligodendrocyte glycoprotein(+) mature oligodendr

168 P4-IgG, pathogenetic serum IgG antibodies to myelin oligodendrocyte glycoprotein, an antigen in the o

169 ls from C57BL/6J mice activated in vivo with myelin oligodendrocyte glycoprotein, Staphylococcal ente

170 ogical disorders with IgG antibodies against myelin-oligodendrocyte glycoprotein (MOG-IgG) have been

171 arge diameter axons and gross aberrations in myelin organization affecting the nodes of Ranvier, the

172 These myelin outfolds surrounded unmyelinated axons, neuronal

173 eflected by the formation of remarkably long myelin outfolds.

174 ytes is not only possible but also increases myelin pattern preservation following demyelination, thu

175 Repeated reorganization of myelin patterns in MS may alter circuit function and con

176 t and metabolism under conditions of chronic myelin phagocytic activity, as TREM2 LOF causes pathogen

177 und that, paradoxically, sterol synthesis in myelin-phagocytosing microglia/macrophages determines th

178 al association with neuronal cell bodies and myelin phagocytosis in the optic tectum.

179 TREM2 senses lipids and mediates myelin phagocytosis, but its role in microglial lipid me

180 Thus, bidirectional manipulation of myelin plasticity functionally affects behavior and neur

181 Together, these results indicate that myelin plasticity induced by modulation of the neonatal

182 Myelin plasticity is critical for neurological function,

183 ytes has been masked by the pathology in the myelin-producing oligodendrocytes, which are lytically d

184 ells after postnatal day 60 has no effect on myelin production and/or oligodendrocyte numbers.

185 ells after postnatal day 60 has no effect on myelin production and/or oligodendrocyte quantities.

186 tures, we demonstrate blocking PAR1 improves myelin production by a mechanism related to effects acro

187 es the number of mature oligodendrocytes and myelin production throughout the remyelination process.

188 duced number of myelinated axons and thinner myelin profiles), as well as substantial focal hypermyel

189 nated axons, neuronal cell bodies, and other myelin profiles.

190 the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes multiple forms of inher

191 y show that the helical tetraspan peripheral myelin protein 22 (PMP22) exhibits a pronounced preferen

192 models overexpressing the PMP22 (peripheral myelin protein 22) protein and in dermal fibroblasts fro

193 y, PERK inactivation reversed attenuation of myelin protein biosynthesis in oligodendrocytes and rest

194 ment, the UPR activation, and attenuation of myelin protein biosynthesis; and resulted in late-onset,

195 Myelin protein P2 is a peripheral membrane protein of th

196 R and ERAD in oligodendrocytes in regulating myelin protein production and maintaining myelin structu

197 ain myelin thickness in adults by regulating myelin protein production.

198 udy, we demonstrate the important role for a myelin protein, myelin and lymphocyte protein (MAL), in

199 d an important decrease in the expression of myelin proteins and a substantial reduction in the perce

200 ination include those that encode structural myelin proteins but also many that encode proteins invol

201 BP) and myelin-associated glycoprotein (MAG) myelin proteins were markedly increased in the cortices

202 dly increased expression of myelin genes and myelin proteins, suggesting a direct induction of genes

203 Myelin proteins, which are produced in the endoplasmic r

204 Here we assess the peripheral myelin proteome by gel-free, label-free mass-spectrometr

205 A much lower mean UTE measure of myelin proton density was found in MS lesions (3.8 mol/L

206 evidence for direct imaging of ultrashort-T2 myelin protons using the UTE sequence.

207 yelin for Diagnostic Imaging provides robust myelin quantification that detects diffuse demyelination

208 for myeloid cell STAT3 in the activation of myelin-reactive T cells and suggests myeloid STAT3 as a

209 s APCs in the thymus and promote deletion of myelin-reactive T cells.

210 apy to reduce brain inflammation and promote myelin recovery in demyelinating diseases.SIGNIFICANCE S

211 godendrocyte progenitor cells maturation and myelin regeneration across the remyelination phase of th

212 s an important regulator of the capacity for myelin regeneration across two experimental murine model

213 ce to define the kinetics and specificity of myelin regeneration after acute oligodendrocyte ablation

214 s essential for Schwann cell myelination and myelin regeneration after nerve injury.

215 Myelin loss limits neurological recovery and myelin regeneration and is critical for restoration of f

216 progressive disability because of failure of myelin regeneration and loss of neurons, suggesting addi

217 STATEMENT Replacement of oligodendroglia and myelin regeneration holds tremendous potential to improv

218 e for development of new clinically relevant myelin regeneration strategies.

219 n is to promote neuroprotection by enhancing myelin regeneration, hence restoring nerve conduction an

220 ght previously unrecognized roles of PAR1 in myelin regeneration, including integrated actions across

221 cal enrichment of this morphogen involved in myelin regeneration.

222 nstrate that knocking out PAR1 also promotes myelin regeneration.

223 ions have been recently been reported in the myelin regulatory factor (MYRF) gene.

224 ctal adenocarcinomas (PDACs) overexpress the myelin regulatory factor (MYRF), an ER membrane-associat

225 ) pups identified an increased expression of myelin-related genes and a decreased expression of immed

226 Rapid myelin imaging correlated with myelin-related stains (proteolipid protein immunostainin

227 r, monocular deprivation results in adaptive myelin remodeling only in parvalbumin-expressing interne

228 ound that both neuron types show homeostatic myelin remodeling under normal vision.

229 itical regulators of primary myelination and myelin repair and suggest that oral GlcNAc may be neurop

230 suggesting novel therapeutic strategies for myelin repair in MS.

231 its functions in peripheral myelination and myelin repair remain elusive.

232 g the generation of new oligodendrocytes for myelin repair.

233 enous progenitors (OPC) which participate in myelin repair.

234 GPR56 controls developmental myelination and myelin repair.

235 cNAc prevents neuro-axonal damage by driving myelin repair.

236 Furthermore, these changes promote myelin restoration and oligodendrocyte maturation throug

237 ation or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characteriz

238 es, lead to severe pathologies, illustrating myelin's crucial role in normal neural functioning.

239 ering of Na(+) channels at the edges of each myelin segment to form nodes of Ranvier.

240 An initial increase in elongation of myelin segments is followed by contraction of a separate

241 nnel clusters along axons that are devoid of myelin segments.

242 In parallel, myelin-sensitive markers decreased in the thalamus, stri

243 Despite the availability of these myelin-sensitive modalities, specificity and sensitivity

244 y action potential conduction depends on the myelin sheath and clustered Na(+) channels at nodes of R

245 s (SCs), thereby forming and maintaining the myelin sheath around peripheral axons (Grove et al., 201

246 arcot-Marie-Tooth neuropathy, but the mature myelin sheath assembly mechanism is unclear.

247 ological events leading to disruption of the myelin sheath in MS.

248 The myelin sheath increases the speed of action potential pr

249 rocyte glycoprotein, an antigen in the outer myelin sheath of central nervous system neurons, are pre

250 (MBP) and its interaction with lipids of the myelin sheath plays an important part in the pathology o

251 ferentiation, oligodendrocyte generation and myelin sheath remodeling in the forelimb motor cortex.

252 In the nervous system, a myelin sheath that originates from oligodendrocytes or S

253 in (MOG), the membrane proteins found in the myelin sheath.

254 tion and maintenance of the peripheral nerve myelin sheath.

255 We performed in vivo two-photon imaging of myelin sheaths along single axons of excitatory callosal

256 can regulate the formation and remodeling of myelin sheaths and perhaps additional functions of oligo

257 Remyelination is the regeneration of myelin sheaths following demyelination.

258 Destruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters

259 ss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as C

260 sticity - affecting oligodendrocytes and the myelin sheaths they produce - that plays a crucial role

261 icity stems from oligodendroglia, which form myelin sheaths to regulate the conduction of nerve impul

262 To determine whether microglia also prune myelin sheaths, we used zebrafish to visualize and manip

263 f surviving oligodendrocytes to generate new myelin sheaths.

264 ligodendrocytes and specifically phagocytose myelin sheaths.

265 of myelin in the brain and showed excellent myelin signal contrast as well as marked ultrashort echo

266 ) rather than decreased diamagnetic (such as myelin) sources.

267 uggests that IFN-gamma responsiveness allows myelin-specific CD8 T cells to optimally perform autoreg

268 Our group has demonstrated that CNS myelin-specific CD8 T cells unexpectedly harbor immune r

269 These results suggest that myelin-specific CD8+ T cells may contribute to disease p

270 Antibody staining along with myelin staining by Luxol-Fast-Blue suggested about 57% o

271 Since the development of cellular and myelin stains, anatomy has formed the foundation for und

272 ecruited MPs being responsible for efficient myelin stripping and clearance and resident MPs being in

273 own-regulated genes required for maintaining myelin structure and the axonal cytoskeleton.

274 entify altered gene expression and disrupted myelin structure as possible mechanisms.

275 ng myelin protein production and maintaining myelin structure using mouse models.

276 Myelin structure, including thickness, was thought to be

277 are essential and necessary for maintaining myelin structure.

278 The betaOHB-induced myelin synthesis occurring together with the marked incr

279 r lactate levels, along with upregulation of myelin-synthesis related genes, collectively resulting i

280 ole for microglia in modifying developmental myelin targeting by oligodendrocytes.

281 ed UPR and ERAD in oligodendrocytes maintain myelin thickness in adults by regulating myelin protein

282 iosynthesis in oligodendrocytes and restored myelin thickness in the CNS of oligodendrocyte-specific

283 inimal myelination defects, no alteration of myelin thickness, and normal KROX20 expression.

284 s and a substantial reduction in the average myelin thickness.

285 ed both reduced ceramide content and reduced myelin thickness.

286 sis; and resulted in late-onset, progressive myelin thinning in the CNS of adult mice (both male and

287 f proteolipid protein production exacerbated myelin thinning in the CNS of oligodendrocyte-specific S

288 s of myelin and the proposed contribution of myelin to CNS plasticity provide possible explanations a

289 We show that the myelin transcription factors (TFs) Myt1 (Nzf2), Myt2 (My

290 This finding replicates in myelin-treated TREM2-deficient murine macrophages and hu

291 Here we show that myelin uptake temporarily skewed these phagocytes toward

292 nd corresponding T2* and T1 of the extracted myelin vesicles provided evidence for direct imaging of

293 SCs clear myelin via autophagy and recent literature has demonstra

294 endoplasmic reticulum (ER) and delivered to myelin via the secretory pathway.

295 UTE measures of myelin were also performed to allow comparison of signal

296 While no obvious changes in myelin were observed at the ultrastructure levels in unc

297 nents in white matter and selectively imaged myelin, which had a measured T2* value of 0.21 msec +/-

298 fear learning instructs the formation of new myelin, which in turn supports the consolidation and/or

299 er is a major challenge in direct imaging of myelin with MRI.

300 tion whereas actin depolymerization promotes myelin wrapping.