Abstract：
:The levels and conformers of alpha-synuclein are critical in the pathogenesis of Parkinson's Disease and related synucleinopathies. Homeostatic mechanisms in protein degradation and secretion have been identified as regulators of alpha-synuclein at different stages of its intracellular trafficking and transcellular propagation. Here we review pathways involved in the removal of various forms of alpha-synuclein from both the intracellular and extracellular environment. Proteasomes and lysosomes are likely to play complementary roles in the removal of intracellular alpha-synuclein species, in a manner that depends on alpha-synuclein post-translational modifications. Extracellular alpha-synuclein is cleared by extracellular proteolytic enzymes, or taken up by neighboring cells, especially microglia and astrocytes, and degraded within lysosomes. Exosomes, on the other hand, represent a vehicle for egress of excess burden of the intracellular protein, potentially contributing to the transfer of alpha-synuclein between cells. Dysfunction in any one of these clearance mechanisms, or a combination thereof, may be involved in the initiation or progression of Parkinson's disease, whereas targeting these pathways may offer an opportunity for therapeutic intervention. This article is part of the Special Issue "Synuclein".
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Stefanis L,Emmanouilidou E,Pantazopoulou M,Kirik D,Vekrellis K,Tofaris GKdoi
10.1111/jnc.14704subject
Has Abstractpub_date
2019-09-01 00:00:00pages
577-590issue
5eissn
0022-3042issn
1471-4159journal_volume
150pub_type
杂志文章,评审abstract：:N alpha-Acyl amino acid releasing enzyme (NAARE), an enzyme cleaving acetylMet-Ala at the Met-Ala bond was purified from rat brain cytosol to apparent homogeneity by salt precipitation, gel filtration, and several steps of ion exchange. Levels of NAARE exceeded acylase measured with acetylmethionine in all brain regio...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb13670.x
更新日期：1983-07-01 00:00:00
abstract：:Perilymph, which bathes the sensory cells of the cochlea, was collected from guinea pigs exposed to noise and analyzed via two cation-exchange HPLC procedures with fluorescence detection, resolving 51 and 81 primary-amine compounds, respectively, at a sensitivity limit of 0.1 pmol relative to leucine. During a first p...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb04745.x
更新日期：1983-08-01 00:00:00
abstract：:The transport kinetics of gamma-aminobutyric acid (GABA), taurine, and beta-alanine in addition to the mutual inhibition patterns of these compounds were investigated in cultures of neurons and astrocytes derived from mouse cerebral cortex. A high-affinity uptake system for each amino acid was demonstrated both in neu...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb04519.x
更新日期：1986-08-01 00:00:00
abstract：:Agmatine (decarboxylated arginine) was originally identified in the CNS as an imidazoline receptor ligand. Further studies demonstrated that agmatine antagonizes NMDA receptors and inhibits nitric oxide synthase. Intrathecally administered agmatine inhibits opioid tolerance and hyperalgesia evoked by inflammation, ner...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04647.x
更新日期：2007-09-01 00:00:00
abstract：:The nervous system is frequently the site of symptomatic toxicity of antineoplastic agents. However, there is limited information about the differential vulnerability of neurons, astrocytes and glioma cells. We have analyzed the effects of four chemotherapeutic drugs (lomustine, cisplatin, topotecan and vincristine) o...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02774.x
更新日期：2004-12-01 00:00:00
abstract：:The effect of a unilateral perinatal hypoxic-ischemic brain injury on dopamine D1 and D2 receptors and uptake sites was investigated in rats by using in vitro quantitative binding autoradiography, 2-3 weeks after the insult. We observed significant decreases in the Bmax and KD for [3H]SCH 23390-labeled D1 and in the B...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb06409.x
更新日期：1991-12-01 00:00:00
abstract：:Recombinant RGS1, RGS16 and RGS-GAIP, but not RGS2, were able to substantially further stimulate the maximal GTPase activity of G(o1)alpha promoted by agonists at the alpha2A-adrenoreceptor in a concentration-dependent manner. Kinetic analysis of the regulation of an alpha2A-adrenoreceptor-G(o1)alpha fusion protein by...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00479.x
更新日期：2001-08-01 00:00:00
abstract：:The delta-opioid receptor is known to regulate multiple effectors in various tissues. When expressed in human embryonic kidney 293 cells, the cloned delta-opioid receptor inhibited cyclic AMP (cAMP) accumulation in response to the delta-selective agonist [D-Pen2,D-Pen5]-enkephalin. The inhibitory response of [D-Pen2,D...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64062700.x
更新日期：1995-06-01 00:00:00
abstract：:Metallothionein (MT)-III, a member of the MT family of metal-binding proteins, is mainly expressed in the CNS and is abundant in glutamatergic neurons. Results in genetically altered mice indicate that MT-III may play neuroprotective roles in the brain, but the mechanisms through which this protein functions have not ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0750266.x
更新日期：2000-07-01 00:00:00
abstract：:Studies in continuously cultured cells have established that familial Alzheimer's disease (FAD) mutant presenilin 1 (PS1) delays exit of the amyloid precursor protein (APP) from the trans-Golgi network (TGN). Here we report the first description of PS1-regulated APP trafficking in cerebral neurons in culture and in vi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04587.x
更新日期：2007-08-01 00:00:00
abstract：:Several analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and screened for their capacity to be oxidized by monoamine oxidase (MAO-A or MAO-B) and their capacity to produce nigrostriatal dopaminergic neurotoxicity in mice. All of the compounds were relatively weak substrates for MAO-A but...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb05606.x
更新日期：1987-03-01 00:00:00
abstract：:In contrast to typical neuroleptic drugs, which have high affinities for dopamine D2 receptors, clozapine binds to multiple neurotransmitter receptors. The mechanisms responsible for its superior clinical efficacy over typical neuroleptics remain unknown. Using an automated genomics approach, total gene expression ana...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00027.x
更新日期：2001-02-01 00:00:00
abstract：:Mutations within the amyloid-beta (Abeta) domain of the amyloid precursor protein (APP) typically generate hemorrhagic strokes and vascular amyloid angiopathy. In contrast, the Arctic mutation (APP E693G) results in Alzheimer's disease. Little is known about the pathologic mechanisms that result from the Arctic mutati...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04443.x
更新日期：2007-05-01 00:00:00
abstract：:45Ca2+ uptake measurements were performed on intact and osmotically lysed synaptosomes from rat brain to study the possible influence of prostaglandins (PGs) on Ca2+ movements into and within the nerve endings. The K+-induced 45Ca2+ uptake of intact synaptosomes was not influenced by several inhibitors of PG synthesis...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb03972.x
更新日期：1982-08-01 00:00:00
abstract：:Complex biological systems are best modeled as highly modular, fluid systems exhibiting a plasticity that allows them to adapt to a vast array of changing conditions. Here we highlight several novel network-based approaches to elucidate genetic networks underlying complex traits. These integrative genomic approaches c...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03661.x
更新日期：2006-04-01 00:00:00
abstract：:Protein aggregation into amyloid fibrils is a key feature of a multitude of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Prion disease. To detect amyloid fibrils, fluorophores with high sensitivity and better efficiency coupled with the low toxicity are in high demand even to date. In this pursuit,...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.15138
更新日期：2020-08-04 00:00:00
abstract：:Explants of adrenal medullae were cultured in defined media for up to 48 h, during which time the tissue remained histologically intact. Addition of N6-methyladenosine to the medium led to a diminution in the activity of phenylethanolamine N-methyltransferase (EC 2.1.1.28) in the tissue. The enzyme activity was invers...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb04705.x
更新日期：1982-07-01 00:00:00
abstract：:Three serine residues (Ser193, Ser194, Ser197) in the fifth transmembrane-spanning region of the D2 dopamine receptor have been mutated separately to alanine and the effects of the mutations determined in ligand-binding experiments with [3H] spiperone. For many antagonists the mutations had little effect, showing that...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.66010394.x
更新日期：1996-01-01 00:00:00
abstract：:The dose-dependent effects of two putative gamma-aminobutyric acid (GABA)-ergic agonists, muscimol and 4,5,6,7-tetrahydroisoxazolo(4,5-e)-pyridin-3-ol (THIP), upon local cerebral glucose utilisation in 60 discrete regions of the CNS have been examined in conscious rats using the [14C]2-deoxyglucose quantitative autora...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb07937.x
更新日期：1982-09-01 00:00:00
abstract：:The endocannabinoid anandamide (N-arachidonoylethanolamine) and other bioactive long-chain N-acylethanolamines are thought to be formed from their corresponding N-acylphosphatidylethanolamines by a specific phospholipase D (NAPE-PLD) in the brain as well as other tissues. However, regional distribution of NAPE-PLD in ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03234.x
更新日期：2005-08-01 00:00:00
abstract：:Networks of neurons express persistent spontaneous network activity when maintained in dissociated cultures. Prolonged blockade of the spontaneous activity with tetrodotoxin (TTX) causes the eventual death of the neurons. In this study, we investigated some molecular mechanisms that may underlie the activity-suppresse...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06204.x
更新日期：2009-08-01 00:00:00
abstract：:Peptide extracts of rat brain powerfully inhibited the cyclic AMP phosphodiesterase activity of rat brain homogenate. Similar extracts of ox brain showed comparable although less potent activity. Preliminary investigation of the physicochemical properties of brain extracts indicated that the rat brain extract containe...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb10881.x
更新日期：1982-01-01 00:00:00
abstract：:The binding of the potent adenosine uptake inhibitor [3H]nitrobenzylthioinosine ([3H]NBI) to brain membrane fractions was investigated. Reversible, saturable, specific, high-affinity binding was demonstrated in both rat and human brain. The KD in both was 0.15 nM with Bmax values of 140-200 fmol/mg protein. Linear Sca...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb04717.x
更新日期：1982-07-01 00:00:00
abstract：:Beta-carbolines have been suggested to be involved in the pathogenesis of Parkinson's disease as a result of their structural similarity to the neurotoxin N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The chloral-derived beta-carboline derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) caus...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.00875.x
更新日期：2002-05-01 00:00:00
abstract：:Exosomes are small extracellular vesicles released by almost all cell types in physiological and pathological conditions. The exosomal potential to unravel disease mechanisms, or to be used as a source of biomarkers, is being explored, in particularly in the field of neurodegenerative diseases. Alzheimer's disease (AD...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/jnc.15112
更新日期：2020-07-03 00:00:00
abstract：:The content, synthesis and transport of D-aspartate (D-Asp) in the CNS of Aplysia californica is investigated using capillary electrophoresis (CE) with both laser-induced fluorescence and radionuclide detection. Millimolar concentrations of D-Asp are found in various regions of the CNS. In the cerebral ganglion, three...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03791.x
更新日期：2006-04-01 00:00:00
abstract：:Autism is a behaviorally defined neurodevelopmental disorder and among its symptoms are disturbances in face and emotional processing. Emerging evidence demonstrates abnormalities in the GABAergic (gamma-aminobutyric acid) system in autism, which likely contributes to these deficits. GABA(B) receptors play an importan...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2010.06858.x
更新日期：2010-09-01 00:00:00
abstract：:When synaptosomes from rat brain were incubated with S-adenosylmethionine (10(-3) M), noradrenaline uptake and KCl-stimulated release were decreased. These effects were dependent on MgCl2, temperature, and incubation time. We have investigated the enzymatic methylation of phosphatidylethanolamine to give phosphatidylc...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb06641.x
更新日期：1982-06-01 00:00:00
abstract：:The N-type voltage-dependent calcium channels play a significant role in neurotransmitter release. The alpha1B subunit of the N-type calcium channel functions as the primary subunit that forms the pore and contains the structural motifs that mediate the pharmacological and gating properties of the channel. We report o...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.731718.x
更新日期：1999-10-01 00:00:00
abstract：:A glutamate binding protein was purified from bovine brain to apparent homogeneity. The procedure used for the purification of this protein involved extraction of a crude synaptic membrane fraction with Na-cholate, followed by solubilization of the binding protein from the membranes by Triton X-100, and, finally, affi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb02691.x
更新日期：1984-02-01 00:00:00
