Abstract:
:Reserch progresses in understanding the pathogenicity of multiple sclerosis (MS) in the last couple of decade has enabled us to develop new drug entities available in the clinic. However, we still have not succeeded in preventing conversion from relapsing-remitting MS (RR-MS) to secondary progressive MS (SP-MS) and curing this intractable form of MS. Furthermore, diagnosis is usually retrospective and subjective, relying on gradual worsening of neurological signs/symptoms. This is obviously due to the lack of understanding for the pathogenicity driving disease progression in MS and of reliable biomarkers reflecting the progressive or stationary disease status. Two relevant components are involved in brain pathology of SP-MS, neurodegeneration and inflammation. Neurodegeneration may occur spontaneously in a neuron-intrinsic manner under chronic inflammation, such as glutamate excitotoxicity, mitochondrial/oxidative injury with iron deposit in the brain, and loss of trophic support. Meanwhile, inflammation is usually associated with recurrent relapse and the cumulative infiltration of immune cells, including T cells, B cells, and myeloid cells of peripheral or CNS origin, could ignite the processes of neurodegeneration. Especially, the higher frequency of leptomeningeal follicle-like structures observed in SP-MS patients suggests that immune cells sheltered behind a blood-brain barrier is still active under smoldering CNS inflammation. Recent successes in Ocrelizumab for primary progressive in MS (PP-MS) and Siponimod for SP-MS reappraised the importance of immune cells for pathogenesis progressive MS. Accordingly, our recent comparative analysis between MS and its animal model, experimental autoimmune encephalomyelitis (EAE), raises a new possibility that ectopic expression of eomesodermin (Eomes) in helper T (Th) cells constitutes a previously unappreciated subset of Th cells with cytotoxic potential against neuronal cells. In this review article, I will summarize the mechanisms proposed on pathogenesis of SP-MS and propose a new pathogenic mechanism for neurodegeneration mediated by unique cytotoxic Th cells.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Oki Sdoi
10.1016/j.neuint.2018.11.023subject
Has Abstractpub_date
2019-11-01 00:00:00pages
104348eissn
0197-0186issn
1872-9754pii
S0197-0186(18)30302-4journal_volume
130pub_type
杂志文章,评审abstract::The influence of alpha2-autoreceptors on the facilitation of [3H]-noradrenaline release mediated by angiotensin II was studied in prostatic portions of rat vas deferens preincubated with [3H]-noradrenaline. Angiotensin II enhanced tritium overflow evoked by trains of 100 pulses at 8 Hz, an effect that was attenuated b...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2006.07.002
更新日期:2006-12-01 00:00:00
abstract::Lipid peroxidation (LP) is a complex process which involves the formation of lipid free radicals and leads to oxidative damage. LP has also been implicated in several neurodegenerative diseases as well as aging. In the present study, we evaluated the effects of the induction of LP in vitro on muscarinic cholinergic (M...
journal_title:Neurochemistry international
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doi:10.1016/0197-0186(93)90133-p
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abstract::The effect of the N-methylisoquinolinium ion (NMIQ(+)) on the activity of enzymes related to metabolism of dopamine was studied using a rat clonal pheochromocytoma PC12h cell line. The activities of tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase (AADC) and monoamine oxidase (MAO) were inhibited by NMIQ...
journal_title:Neurochemistry international
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doi:10.1016/0197-0186(89)90138-1
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abstract::Neosurugatoxin, a neurotoxin isolated from the Japanese ivory mollusc (Babylonia japonica ) is a nicotinic antagonist with a specificity towards ganglionic nicotinic receptors. At low concentration (5 x 10(?8) M) neosurugatoxin inhibited the release of [(3)H]dopamine evoked by 1,1-dimethyl-4-phenylpiperazinium (DMPP) ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(85)90131-7
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abstract::Purified synaptic vesicles were isolated from hog cerebral cortex by a rapid procedure consisting of homogenization of cerebral cortex slices in iso-osmotic sucrose, differential centrifugation and sucrose density-gradient centrifugation. The purity of the vesicles was evaluated both biochemically and morphologically....
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(83)90095-5
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abstract::Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder and is characterized by pathological aggregates of amyloid β-protein (Aβ) and tau protein. On the basis of genetic evidence, biochemical data, and animal models, Aβ has been suggested to be responsible for the pathogenesis of AD (the am...
journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/j.neuint.2017.08.010
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abstract::Platelet-activating factor (PAF), a biologically active lipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphoholine), is identified in different regions of brain, including hippocampus. Specific PAF-activated receptors (PAFRs) are expressed in corresponding brain areas. PAF has been proposed to be a retrograde messenger of l...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(03)00126-8
更新日期:2004-02-01 00:00:00
abstract::Receptors for transmitters, as varied as those expressed by neurons, have been described on primary astrocyte cultures prepared from new-born rats and mice. A variety of functional effects and considerable cell-to-cell and regional heterogeneity have been observed for such receptors in vitro. The various systems avail...
journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/0197-0186(94)00118-e
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2011.10.005
更新日期:2011-12-01 00:00:00
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(03)00013-5
更新日期:2003-09-01 00:00:00
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journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/0197-0186(92)90224-f
更新日期:1992-03-01 00:00:00
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(82)90044-4
更新日期:1982-01-01 00:00:00
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(94)90045-0
更新日期:1994-07-01 00:00:00
abstract::Taurine-like immunoreactivity (TLI) is found in the pigeon retina at high levels within cones, in select cells of the inner nuclear layer and in sublaminae of the inner plexiform layer. At the ultrastructural level a high density of immuno-gold particles in visualized in the ellipsoid, but not in the paraboloid area o...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(95)00043-8
更新日期:1995-12-01 00:00:00
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(99)00046-7
更新日期:1999-05-01 00:00:00
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(90)90104-2
更新日期:1990-01-01 00:00:00
abstract::The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PE3/AM by a cooled CCD imaging analysis system. Electron microscopic obse...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2005.12.012
更新日期:2006-06-01 00:00:00
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(01)00052-3
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2007.08.005
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journal_title:Neurochemistry international
pub_type: 杂志文章,评审
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journal_title:Neurochemistry international
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pub_type: 杂志文章
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2011.02.010
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journal_title:Neurochemistry international
pub_type: 杂志文章,评审
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journal_title:Neurochemistry international
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journal_title:Neurochemistry international
pub_type: 杂志文章,评审
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journal_title:Neurochemistry international
pub_type: 杂志文章
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journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/s0197-0186(02)00030-x
更新日期:2002-08-01 00:00:00
abstract::Açai (Euterpe oleracea Mart.), a highly consumed fruit in Amazon, is from a common palm with remarkable antioxidant properties. Because oxidative stress and seizures are intimately linked, this study investigated the potential neuroprotective and anticonvulsant effects of commercial clarified açai juice (EO). EO did n...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2015.06.014
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abstract::Allosteric modulation of [3H]strychnine binding to glycine receptors (GlyRs) was examined in synaptosomal membranes of rat spinal cord. An allosteric model enabled us to determine the cooperativity factors of the allosteric agents with [3H]strychnine and glycine bindings (alpha and beta, respectively). We modified the...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2003.08.010
更新日期:2004-06-01 00:00:00