Abstract:
:Recent evidence indicates that protein aggregation and in particular the formation of toxic protein oligomers is a key mechanism in synucleinopathies such as Parkinson's disease (PD). Post mortem brain tissue studies as well as animal studies furthermore suggest that matrix metalloproteinases (MMPs) are also involved in the pathogenesis of PD. We used confocal single molecule spectroscopy to characterize the influence of MMPs and other proteases on the aggregation of alpha-synuclein. These studies were complemented by the characterization of alpha-synuclein fragment patterns generated by these proteases using gel electrophoresis and mass spectrometry. Limited digestion by MMP-1 and MMP-3, but not by MMP-9, increased the tendency of alpha-synuclein to aggregate. Proteinase K and Trypsin did not increase the level of de novo aggregation of alpha-synuclein. SDS-PAGE as well as MALDI-ToF analysis of limitedly digested alpha-synuclein demonstrate that all proteases generate different fragments of alpha-synuclein. We provide mass spectrometry data of proteolytic alpha-synuclein fragments and propose specific cleavage sites for MMP-1 and MMP-9 in alpha-synuclein. We furthermore found four additional cleavage sites of MMP-3 that had not been described previously. In order to increase aggregation of alpha-synuclein, specific cleavage between the highly charged C-terminal domain and the aggregation-prone NAC domain of alpha-synuclein seems to be crucial. Our findings obtained in vitro in a well-characterized model of pathological alpha-synuclein aggregation indicate that MMP-1 and MMP-3 may also influence pathogenesis of PD in vivo by generation of specific aggregation-enhancing alpha-synuclein fragments resulting from limited proteolysis.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Levin J,Giese A,Boetzel K,Israel L,Högen T,Nübling G,Kretzschmar H,Lorenzl Sdoi
10.1016/j.expneurol.2008.10.010subject
Has Abstractpub_date
2009-01-01 00:00:00pages
201-8issue
1eissn
0014-4886issn
1090-2430pii
S0014-4886(08)00405-6journal_volume
215pub_type
杂志文章abstract::After injury of their axons, damaged neurons shift their metabolic activity into a reparative mode aimed at survival and regeneration or, alternatively, they undergo degeneration and die. Previous reports have shown that at the initial stages of the response to axonal injury, polyamines are essential for neuronal surv...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(86)90307-9
更新日期:1986-06-01 00:00:00
abstract::Triggering receptor expressed on myeloid cells-2 (TREM2) was a newly identified receptor expressed on microglia. Several observations support the hypothesis that TREM2 variation may confer susceptibility to Parkinson's disease (PD). Therefore, in this paper, we explored the role of TREM2 in the 1-methyl-4-phenyl-1,2,3...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2018.01.016
更新日期:2018-04-01 00:00:00
abstract::Diffuse axonal injury is thought to be the basis of the functional impairments stemming from mild traumatic brain injury. To examine how axons are damaged by traumatic events, such as motor vehicle accidents, falls, sports activities, or explosive blasts, we have taken advantage of the spinal cord with its extensive w...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2015.04.023
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::Glomerular convergence has been proposed to rely on interactions between like olfactory axons, however topographic targeting is influenced by guidance molecules encountered in the olfactory bulb. Disruption of these cues during development misdirects sensory axons, however little is known about the role of bulb-derive...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.06.022
更新日期:2007-10-01 00:00:00
abstract::The accumulation of damage to DNA plays a significant role in the etiology of the aging process. The importance of nutrition in delaying the aging process is well recognized. L-carnitine is a quaternary ammonium compound heterogeneously distributed in the brain. In the present study the effect of L-carnitine on DNA da...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.09.009
更新日期:2005-01-01 00:00:00
abstract::Intranuclear inclusion bodies are a shared pathological feature of Huntington's disease (HD) and its transgenic mouse model. Using a panel of antibodies spanning the entire huntingtin molecule, we have investigated the pattern of immunoreactivity within the intranuclear inclusions in the frontal cortex and striatum of...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1998.7005
更新日期:1999-03-01 00:00:00
abstract::Functional regeneration of brainstem-spinal pathways occurs in the developing chick when the spinal cord is severed prior to embryonic day (E) 13. Functional spinal cord regeneration is not observed in animals injured after E13. This developmental transition from a permissive to a restrictive repair period may be due ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7496
更新日期:2000-11-01 00:00:00
abstract::Systemic administration of the amphetamine derivative p-chloroamphetamine (PCA) causes degeneration of 5-HT axon terminals in rat brain. The present study was designed to determine whether PCA induces neurotoxic effects by a direct action on 5-HT axon terminals. PCA was administered by microinjection directly into the...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(05)80015-9
更新日期:1990-09-01 00:00:00
abstract::The release of reactive oxygen species (ROS) by neutrophils, which infiltrate the region of damage following spinal cord injury (SCI), was investigated to determine if such release is significant following spinal cord injury. The relationship of extracellular levels of hydroxyl radicals and hydrogen peroxide obtained ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.05.046
更新日期:2004-12-01 00:00:00
abstract:RATIONALE:Neurofibromatosis type 1 (NF1) is associated with higher rates of epilepsy compared to the general population. Some NF1 patients with epilepsy do not have intracranial lesions, suggesting the genetic mutation itself may contribute to higher rates of epilepsy in these patients. We have recently demonstrated in...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2020.113373
更新日期:2020-09-01 00:00:00
abstract::c-fos expression in response to noxious mechanical stimulation of the peripheral receptive field was used to study the somatotopic representation of the oral mucous membrane and trigeminal cutaneous receptive fields in the trigeminal subnucleus caudalis and the cervical spinal dorsal horn. Fos-neurons (neurons with c-...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1994.1167
更新日期:1994-10-01 00:00:00
abstract::Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2017.03.024
更新日期:2017-07-01 00:00:00
abstract::c-Fos protein-like immunoreactivity (IR) was investigated in the rat brain following an application of weak anodal direct current to the surface of the unilateral sensorimotor cortex in an attempt to elucidate the cellular and molecular bases of central plasticity. Anodal polarization resulted in a massive increase in...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1995.1004
更新日期:1995-05-01 00:00:00
abstract::We previously reported that 1 month following unilateral loss (>95%) of striatal dopamine, there is an increase in striatal glutamate function as measured by in vivo microdialysis and quantitative immuno-gold electron microscopy, Neuroscience 88, 1-16). The goal of this study was to determine the effect of bilateral l...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(02)00050-x
更新日期:2003-03-01 00:00:00
abstract::The cell death induced by hydroxyl radicals generated by Cu-phenanthroline and peroxynitrite generated by 3-morpholinosydnonimine hydrochloride (SIN-1) in rat primary cortical neuronal cultures was compared with the apoptotic death induced by staurosporine and the necrotic death induced by glutamate. Both SIN-1 and Cu...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7322
更新日期:2000-03-01 00:00:00
abstract::Accumulating evidence shows alterations in the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) in ALS patients and in animal models of disease, mainly by endothelial cell (EC) damage. Repair of the altered barrier in the CNS by replacement of ECs via cell transplantation may be a new therapeutic approac...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2018.08.012
更新日期:2018-12-01 00:00:00
abstract::A prospective, multicenter, randomized trial did not demonstrate improved outcomes in severe traumatic brain injured patients treated with mild hypothermia [Clifton, G.L., Miller, E.R., Choi, S.C., Levin, H.S., McCauley, S., Smith, K.R., Jr., Muizelaar, J.P., Wagner, F.C., Jr., Marion, D.W., Luerssen, T.G., Chesnut, R...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.09.024
更新日期:2009-01-01 00:00:00
abstract::We compared the magnetic cerebral activity of 10 fetal subjects at two different gestational ages. Spontaneous cerebral activity was recorded with a large array magnetometer specially designed to conform to the maternal gravid abdomen during the third trimester of pregnancy. We recorded each fetal subject at least twi...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.06.026
更新日期:2004-11-01 00:00:00
abstract::As part of a wider investigation on brain structure and function in young rats with inherited hydrocephalus, this study was undertaken to develop a technique to monitor, and quantify, progressive changes in ventricle and cortical dimensions in hydrocephalic rats in vivo. Magnetic resonance images were obtained with a ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(92)90016-j
更新日期:1992-10-01 00:00:00
abstract::In this study, the effects of testosterone propionate (TP) on recovery from facial paralysis following crush axotomy of the facial nerve in male hamsters were examined. In the first experiment, TP (5 mg/ml sesame oil; 0.1 ml) was injected subcutaneously and on alternate days in one-half of the animals subjected to cru...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(89)90174-x
更新日期:1989-07-01 00:00:00
abstract::Paclitaxel is an effective chemotherapeutic agent that, despite its common use, often causes peripheral sensory neuropathy. In neurons, paclitaxel binds to and stabilizes microtubules, and through unknown mechanisms, bundles microtubules and disrupts their organization. Because microtubules serve as tracks on which a ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2015.06.023
更新日期:2015-09-01 00:00:00
abstract::Following a unilateral fimbria-fornix lesion, the delivery of nerve growth factor (NGF) to the ipsilateral lateral ventricle of the rat can prevent the lesion-induced loss of choline acetyltransferase (ChAT) expression in the ipsilateral medial septum and vertical diagonal band region. In the present study, the abilit...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(90)90049-x
更新日期:1990-10-01 00:00:00
abstract::Dentate gyrus is usually assumed to be resistant to ischemia. However, the mechanisms underlying this functional plasticity are not fully understood. Herein, we aimed at identifying a neuroprotective mechanism in the dentate gyrus of the adult rat after global ischemia. Cyclic AMP response element (CRE)-binding protei...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.06.016
更新日期:2006-12-01 00:00:00
abstract::We have analyzed a mouse model of Charcot-Marie-Tooth disease 2E (CMT2E) harboring a heterozygous p.Asn98Ser (p.N98S) Nefl mutation, whose human counterpart results in a severe, early-onset neuropathy. Behavioral, electrophysiological, and pathological analyses were done on separate cohorts of NeflN98S/+ mutant mice a...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2018.06.010
更新日期:2018-10-01 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::Fluoxetine is one of the most promising drugs for improving clinical outcome in patients with ischemic stroke. This in vivo study investigated the hypothesis that fluoxetine may affect HIF-1α-Netrin/VEGF cascade, angiogenesis and neuroprotection using a rat model of transient middle cerebral artery occlusion (tMCAO). ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2020.113312
更新日期:2020-07-01 00:00:00
abstract::Infantile spasms are generalized convulsive seizures seen in the first year of life. They respond poorly to conventional anticonvulsants, but are often controlled by adrenocorticotropic hormone (ACTH) therapy. Other childhood seizures are also responsive to ACTH. The present study tested the effects of ACTH and relate...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2002.7874
更新日期:2002-05-01 00:00:00
abstract::Diffuse and neuritic plaques are sites of accumulation of beta-amyloid peptides (A beta) in the brains of Alzheimer's disease (AD) patients. Although amyloid fibrils are formed from A beta, the contribution of other plaque-associated proteins and peptides to the pathogenesis of AD amyloidosis is unknown. To pursue thi...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1994.1209
更新日期:1994-12-01 00:00:00
abstract::Our results indicate that Long-Evans male rats housed in standard conditions show no significant difference between the areas of sections of their left and right amygdalas. In contrast, the S1 strain maze-bright animals have a significantly greater right amygdala than left. Furthermore, the data indicate an overall in...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(84)90187-0
更新日期:1984-11-01 00:00:00