Abstract：
:Parkinson's disease (PD) is characterized by the polymerization of wild-type (WT) or mutant alpha-synuclein (AS) into aggregates and fibrils, which are observed as Lewy bodies (LBs) and Lewy neurites (LNs) in PD patients. However, inability to demonstrate aggregation in many cell culture systems is a major drawback for effective in vitro modeling of AS aggregation. Utilizing PCR-based cloning approach, we generated A30P, A53T, and the recently reported E46K encoding mutation in the KTKEGV repeat region of AS gene. While cloning E46K mutant, a glycine deletion mutation (E46KDeltaG) adjacent to the intended lysine mutation was serendipitously generated. Expression of mutant constructs and green fluorescent protein (GFP)-tagged mutant constructs in catecholaminergic SH-SY5Y (5Y) cells revealed 40% of AS-E46KDeltaG and 18% of AS-E46K transfected cells formed aggregates as compared to 12% in AS-A53T, 6% in AS-WT, and 2% in AS-A30P transfected cells. Western blot analysis demonstrated the formation of high molecular weight AS aggregates. Electron microscopic analysis of 5Y cells expressing the E46K and E46KDeltaG mutants demonstrated two distinct kinds of inclusions: Type I, which showed dense granular profile; and Type II, which were largely membranous vacuolar inclusions without granular material. These two inclusions are reminiscent of Lewy bodies and pale bodies observed in PD postmortem brain samples. Our results demonstrate that mutations in 4th KTKEGV repeat lead to higher propensity of aggregation of AS compared to other mutants.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Pandey N,Schmidt RE,Galvin JEdoi
10.1016/j.expneurol.2005.10.019keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
515-20issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(05)00378-Xjournal_volume
197pub_type
杂志文章abstract：:We studied local autoimmune reactions in rat sciatic nerve after two successive injuries at the same site. The behavioral consequences of these injuries were also examined. We found that repetitive injuries had a moderately adverse effect on function and were accompanied by local autoimmune reactions. A causal relatio...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(85)90200-6
更新日期：1985-05-01 00:00:00
abstract：:Caspases are cysteine proteases involved in apoptotic cell death, and pharmacological caspase inhibition has been demonstrated to prevent neuronal cell death in certain experimental paradigms. In this study, the role of caspase-1 and -3 in the death of dopaminergic neurons derived from the E14 rat ventral mesencephalo...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2001.7749
更新日期：2001-09-01 00:00:00
abstract：:Experimental tumors of the central nervous system were investigated with antibodies to quinolinate to assess the cellular distribution of this endogenous neurotoxin. In advanced F98 and RG-2 glioblastomas and E367 neuroblastomas in the striatum of rats, variable numbers of quinolinate immunoreactive cells were observe...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1996.6365
更新日期：1997-04-01 00:00:00
abstract：:This study was undertaken as part of the NIH "Facilities of Research-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeated a study reporting that a combinatorial treatment with transplants of Schwann cells, systemic delivery of Rolipram to enhance cyclic AMP levels, and...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2010.12.020
更新日期：2012-02-01 00:00:00
abstract：:A new method is presented for the quantification of cell viability based on densitometry with computerized image analysis. Neuronal cells were stained with crystal violet and densitometric analysis was performed with an IBAS 2.0 image analyzer (Kontron/ Zeiss), using specially implemented dedicated software which inte...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1997.6647
更新日期：1997-11-01 00:00:00
abstract：:In mammals, free d-aspartate (D-Asp) is abundant in the embryonic brain, while levels remain very low during adulthood as a result of the postnatal expression and activity of the catabolizing enzyme d-aspartate oxidase (DDO). Previous studies have shown that long-lasting exposure to nonphysiological, higher D-Asp conc...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2019.02.014
更新日期：2019-07-01 00:00:00
abstract：:Proximal axotomy in adult animals results in delayed death of motor neurons. Features characteristic of both necrosis and apoptosis have been described in motor neurons of the spinal cord following proximal avulsion of the ventral roots. We have previously demonstrated that a genomic herpes simplex virus (HSV)-based v...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2000.7597
更新日期：2001-04-01 00:00:00
abstract：:We recently reported structural changes in nodes of Ranvier of frog dorsal roots that are associated with activation at 20 or 50 Hz for 15 min. The structural effects co-occur with alterations in the latency, amplitude, and waveform of the compound action potential. The alterations in nodal morphology include formatio...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(88)90067-2
更新日期：1988-07-01 00:00:00
abstract：:The aim of this study was to examine whether acute nerve compression damages an axonal transport system based on microtubules and how the fibers recover after the compression. A 5-mm segment of the tibial nerve of male wistar rat was compressed with a specially designed clip. Functional recovery was assessed using Tib...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1997.6601
更新日期：1997-10-01 00:00:00
abstract：:Motor nerve conduction velocity was measured in six branches of the sciatic nerve in streptozotocin-diabetic rats. It was markedly reduced in nerves to the gastrocnemius, soleus, tibialis anterior, and extensor digitorum longus muscles. The branch to the plantaris muscle remained unaffected. In control rats none of th...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(86)90315-8
更新日期：1986-06-01 00:00:00
abstract：:Administration of endogenous corticosterone to intact animals induces calbindin-D28k protein in the hippocampal CA1-CA2 subfields. The fact that this effect on calbindin-D28k was shown to be specific for the hippocampus argues for a receptor-mediated effect on gene expression. In addition, chronic pretreatment with co...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1997.6729
更新日期：1998-02-01 00:00:00
abstract：:The functional and morphologic consequences of treatment of peripheral nerve lesions with exogenous 3,3',5-triiodo-L-thyronine (T3) are unclear. In this study adult Wistar rats with sciatic nerve crush lesions were treated with 20 micrograms/kg/day of T3. The treated animals gained weight though more slowly than vehic...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(86)90077-4
更新日期：1986-02-01 00:00:00
abstract：:Traumatic CNS injury triggers a systemic inflammatory response syndrome (SIRS), in which circulating inflammatory cells invade body organs causing local inflammation and tissue damage. We have shown that the SIRS caused by spinal cord injury is greatly reduced by acute intravenous treatment with an antibody against th...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2015.07.003
更新日期：2015-09-01 00:00:00
abstract：:Despite the importance of the periaqueductal gray (PAG) in the modulation of nociception and pain, many aspects of the roles of the different columns of the PAG in descending controls: facilitation and inhibition, are not understood. Employing a tonic muscle pain model established by i.m. injection of 5.8% saline into...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2014.04.019
更新日期：2014-07-01 00:00:00
abstract：:Adenoviral-mediated gene transfer to the caudate nucleus of Macaca mulatta was accomplished using stereotactic injection of two distinct recombinant Ad5 vectors containing the gene for Escherichia coli beta-galactosidase and the cDNA for rat hypoxanthine-guanine phosphoribosylphosphotransferase (HPRT), respectively. M...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1994.1028
更新日期：1994-02-01 00:00:00
abstract：:The transformation of a cut axonal end into a growth cone (GC), after axotomy, is a critical event in the cascade leading to regeneration. In an earlier series of studies we analyzed the cellular cascades that transform a cut axonal end into a competent GC. We found that axotomy of cultured Aplysia neurons leads to a ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2009.05.004
更新日期：2009-09-01 00:00:00
abstract：:SCI is followed by dramatic upregulation of chondroitin sulfate proteoglycans (CSPGs) which limit axonal regeneration, oligodendrocyte replacement and remyelination. The recent discovery of the specific CSPGs signaling receptor protein tyrosine phosphatase sigma (RPTPσ) provided an opportunity to refine the therapeuti...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2018.08.003
更新日期：2018-11-01 00:00:00
abstract：:Studies of the effects of lesions of the parietal cortex suggest that this region plays a critical role in visuomotor guidance, whereas experiments on the effects of disconnecting this region from visual input have been inconsistent in supporting this hypothesis. In the present experiment, monkeys with a unilateral oc...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(83)90161-9
更新日期：1983-07-01 00:00:00
abstract：:The role of central noradrenergic neurons in kindled seizures was assessed by comparison of alpha 2- and beta-adrenoceptor binding in the cerebral cortex from kindled and control rats. To minimize handling, which may modify kindling-induced changes in binding, the kindling protocol involved stimulation of the amygdala...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(85)90044-5
更新日期：1985-10-01 00:00:00
abstract：:Among endogenous adaptive systems to hypoxia, neuroglobin, a recently discovered heme protein, was suggested as a novel oxygen-dependent neuroprotectant. We aimed to characterize i) maturational age-related regulation of neuroglobin in the developing mouse brain under normoxic and hypoxic conditions, and ii) the role ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2012.04.006
更新日期：2012-07-01 00:00:00
abstract：:Cannabis abuse may precipitate the onset of schizophrenia and a dysfunction of the endocannabinoid system may be involved in the pathology of schizophrenia. Nevertheless, only few studies have addressed the neurobiological consequences of cannabis abuse for the development and course of schizophrenia. We measured the ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2007.02.004
更新日期：2007-05-01 00:00:00
abstract：:Primary spinal cord trauma can initiate a cascade of pathophysiologic events which markedly contribute to the expansion and amplification of the primary insult. The detailed mechanisms of these secondary neurochemical reactions are largely unknown; however, they involve membrane lipid derangements with the release of ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1999.7308
更新日期：2000-02-01 00:00:00
abstract：:Mitochondria play a pivotal role in the cascade of events associated with cell death pathways that are involved with several forms of neurodegeneration. Recent findings show that in the Bax/Bak-dependent pathway of apoptosis, the release of cytochrome c from mitochondria is a consequence of two carefully coordinated e...
journal_title：Experimental neurology
pub_type： 杂志文章,评审
doi：10.1016/j.expneurol.2009.05.021
更新日期：2009-08-01 00:00:00
abstract：:The binding of agonists and antagonists to beta-adrenergic receptors in brain tissue obtained postmortem in nonalcoholic controls and matched intoxicated and sober alcoholics was measured to assess the state of the receptors and their coupling to adenylate cyclase. Binding of antagonist, iodocyanopindolol, to cerebral...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(89)90131-3
更新日期：1989-09-01 00:00:00
abstract：:We investigated the involvement of central nervous system nicotinic-acetylcholine receptors in the secretory activity of the hypothalamic-hypophyseal-adrenal axis. Antiacetylcholine receptor antibodies derived from rabbits immunized with purified Torpedo-acetylcholine receptor or from myasthenia gravis patients were i...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(86)90251-7
更新日期：1986-12-01 00:00:00
abstract：:Using an approach that combines gene therapy with aromatic l-amino acid decarboxylase (AADC) gene and a pro-drug (l-dopa), dopamine, the neurotransmitter involved in Parkinson's disease, can be synthesized and regulated. Striatal neurons infected with the AADC gene by an adeno-associated viral vector can convert perip...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2000.7408
更新日期：2000-07-01 00:00:00
abstract：:Recent in vitro studies have shown that the periventricular subependymal zone (SEZ) of the rodent brain is capable of de novo generation of neurons and glia. There is less information available on neurogenesis in the adult human brain, and no study has shown the clonal generation of neurons and glia from in vitro-gene...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1999.7028
更新日期：1999-04-01 00:00:00
abstract：:Stress and glucocorticoids exacerbate pain via undefined mechanisms. Macrophage migration inhibitory factor (MIF) is a constitutively expressed protein that is secreted to maintain immune function when glucocorticoids are elevated by trauma or stress. Here we show that MIF is essential for the development of neuropath...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2012.04.018
更新日期：2012-08-01 00:00:00
abstract：:Axonal injury is present in essentially all clinically significant cases of traumatic brain injury (TBI). While no effective treatment has been identified to date, experimental TBI models have shown promising axonal protection using immunosuppressants FK506 and Cyclosporine-A, with treatment benefits attributed to cal...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2016.06.011
更新日期：2016-09-01 00:00:00
abstract：:Muscle disuse-induced changes in the cholinergic system of sciatic nerve, slow-twitch soleus (SOL), and fast-twitch extensor digitorum longus (EDL) muscles were studied in rats. Rats with hind limbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase in sciatic nerve (38%), ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(85)90012-3
更新日期：1985-09-01 00:00:00
