Abstract:
:Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disorder. AD is mostly a sporadic disorder and its main risk factor is age, but mutations in three genes that promote the accumulation of the amyloid-β (Aβ42) peptide revealed the critical role of amyloid precursor protein (APP) processing in AD. Neurofibrillary tangles enriched in tau are the other pathological hallmark of AD, but the lack of causative tau mutations still puzzles researchers. Here, we describe the contribution of a powerful invertebrate model, the fruit fly Drosophila melanogaster, to uncover the function and pathogenesis of human APP, Aβ42, and tau. APP and tau participate in many complex cellular processes, although their main function is microtubule stabilization and the to-and-fro transport of axonal vesicles. Additionally, expression of secreted Aβ42 induces prominent neuronal death in Drosophila, a critical feature of AD, making this model a popular choice for identifying intrinsic and extrinsic factors mediating Aβ42 neurotoxicity. Overall, Drosophila has made significant contributions to better understand the complex pathology of AD, although additional insight can be expected from combining multiple transgenes, performing genome-wide loss-of-function screens, and testing anti-tau therapies alone or in combination with Aβ42.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Fernandez-Funez P,de Mena L,Rincon-Limas DEdoi
10.1016/j.expneurol.2015.05.013subject
Has Abstractpub_date
2015-12-01 00:00:00pages
58-71issue
Pt Aeissn
0014-4886issn
1090-2430pii
S0014-4886(15)00169-7journal_volume
274pub_type
杂志文章,评审abstract::The increasing demand on diagnostic assays that are sensitive and specific for pathogenic antibodies, and the interest in identifying new antigens, prompted the development of cell-based assays for the detection of autoantibodies in myasthenia gravis and other autoimmune disorders. Cell-based assays were initially use...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2015.01.011
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:Novel strategies to improve hand function after stroke are needed. Electromyography-triggered functional neuromuscular stimulation (EMG-FNMS) and repetitive transcranial magnetic stimulation (rTMS) are promising techniques to facilitate recovery of sensory-motor hand dysfunction after stroke. OBJECTIVE:To i...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.04.010
更新日期:2011-07-01 00:00:00
abstract::Regeneration in the peripheral nervous system offers unique opportunities and challenges to medicine. Compared to the central nervous system, peripheral axons can and do regenerate resulting in functional recovery, especially if the distance to target is short as in distal limb injuries. However, this regenerative cap...
journal_title:Experimental neurology
pub_type: 社论
doi:10.1016/j.expneurol.2009.12.001
更新日期:2010-05-01 00:00:00
abstract::The regulation of perinatal glia limitans (GL) reformation by interleukin-1beta (IL-1beta) following prenatal neural trauma in the mouse was studied in lesioned fetal mice by immunocytochemistry and computer-assisted image analysis for presence and distribution of astrocytes and IL-1beta immunoreactivity (ir). Astrocy...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6470
更新日期:1997-06-01 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::To determine whether or not brain damage is likely to occur in the repeated apneic episodes experienced by some alcoholics during intoxicated sleep, rats were anesthetized with alcohol and subjected to repeated episodes to asphyxia. Each episode lasted 90 s, arterial PO2 was less than 50 mm Hg for 60 s, and 30 episode...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(84)90017-7
更新日期:1984-04-01 00:00:00
abstract::Dorsal root ganglia (DRG) neuronopathy was induced in rats by chronic treatment (2 mg/kg twice a week for nine injections) with the antineoplastic drug cisplatin. Morphological alterations and changes in peptide [calcitonin gene-related peptide (CGRP), substance P, galanin (Gal), and somatostatin] concentration were s...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1996.0050
更新日期:1996-03-01 00:00:00
abstract::As early as 1928, Cajal suggested that plaques contain a trophic substance which attracts neurites. Recently, basic fibroblast growth factor (bFGF) levels were shown to be elevated in Alzheimer's disease (AD) and localized to plaques and neurofibrillary tangles. We sought to clarify the subtype of plaques which contai...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1993.1202
更新日期:1993-12-01 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::With the use of four independent cell markers and Brd-U birthdating we have charted the earliest stages of neuronal differentiation and migration in the developing rat central nervous system, including the cortex, spinal cord, and retina. One of the markers, the monoclonal antibody 2G12, labeled a large subpopulation ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1995.1031
更新日期:1995-07-01 00:00:00
abstract::Stimulation of peripheral nerves activates corresponding regions in sensorimotor cortex. We have applied functional magnetic resonance imaging (fMRI) techniques to monitor activated brain regions by means of measuring changes of blood oxygenation level-dependent contrast during electric stimulation of the forepaw, hin...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7524
更新日期:2000-12-01 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::C2 spinal cord hemisection results in synaptic and astroglial changes in the phrenic nucleus which have been associated with the recovery of the ipsilateral hemidiaphragm during expression of the crossed phrenic phenomenon. As part of our ongoing analysis of the neurotransmitters involved, the present study investigat...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1999.7238
更新日期:1999-12-01 00:00:00
abstract::Historically, the immune response after spinal cord injury was considered largely detrimental owing to the release of neurotoxic factors. While there is validity to this view, there is much greater heterogeneity of immune cells than was previously realized. Associated with this heterogeneity of immune cell subtypes, t...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2014.01.025
更新日期:2014-08-01 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::Exposing rat dorsal root ganglion (DRG) neurons to dibutyryl cAMP (db-cAMP) enables central branches to regenerate in the spinal cord by nullifying the ability of CNS myelin to inhibit elongation. A conditioning lesion (CL) promotes similar regeneration of central branches in the spinal cord by increasing neuronal cAM...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.03.010
更新日期:2004-10-01 00:00:00
abstract::We have previously shown that lesions of the sensorimotor cortex induced by either thermocoagulation or aspiration produce different effects on axonal plasticity. We have now investigated whether these methods of lesion also influence the behavioral outcome. The behavioral effects of unilateral and bilateral lesions o...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1998.6893
更新日期:1998-11-01 00:00:00
abstract::Oscillatory activity has been well-studied in many structures within cortico-basal ganglia circuits, but it is not well understood within the pedunculopontine nucleus (PPN), which was recently introduced as a potential target for the treatment of gait and postural impairments in advanced stages of Parkinson's disease ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2016.05.007
更新日期:2016-08-01 00:00:00
abstract::Chewing rhythms are set by a putative central pattern generator whose output is influenced by sensory feedback. In this study we assessed how an altered feedback imposed by changing the hardness of a gum bolus modifies the timing of chewing, the maximal gape, and the activity in the masseter muscle on the chewing side...
journal_title:Experimental neurology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0014-4886(86)90292-x
更新日期:1986-06-01 00:00:00
abstract::The present study evaluates the temporal relationships between increases in glial fibrillary acidic protein (GFAP) mRNA, GFA protein levels, and GFAP immunostaining in the hippocampus of adult rats following unilateral lesions of the entorhinal cortex (EC). GFAP mRNA levels were assessed at 12 h, 1, 2, 4, 6, 8, 10, 12...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1993.1187
更新日期:1993-12-01 00:00:00
abstract::By way of commentary on a recent report that transplanted adult neural progenitor cells can alleviate functional deficits in a rat lesion model of Huntington's disease [Vazey, E.M., Chen, K., Hughes, S.M., Connor, B., 2006. Transplanted adult neural progenitor cells survive, differentiate and reduce motor function imp...
journal_title:Experimental neurology
pub_type: 评论,杂志文章,评审
doi:10.1016/j.expneurol.2006.11.007
更新日期:2007-02-01 00:00:00
abstract::Traumatic brain injuries (TBI) sustained during peri-adolescent development produce lasting neuro-behavioral changes that render individuals at an increased risk for developing substance abuse disorders. Experimental and clinical evidence of a prolonged period of hypodopaminergia after TBI have been well documented, b...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2017.08.003
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:Intracerebral hemorrhage (ICH) is the common brain diseases in middle-aged and elderly people, with high disability and/or mortality rate, and is a serious public health concern. Both WNK3 kinase and the WNK3/SPAK/NKCC1 signaling pathway play an integral role in maintaining normal cell homeostasis. However, ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2020.113386
更新日期:2020-10-01 00:00:00
abstract::This article reviews stem cell-based strategies for spinal cord injury repair, and practical issues concerning their translation to the clinic. Recent progress in the stem cell field includes clinically compliant culture conditions and directed differentiation of both embryonic stem cells and somatic stem cells. We pr...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2007.09.002
更新日期:2008-02-01 00:00:00
abstract::We examined the response of neuronal nitric oxide synthase (nNOS)-containing CNS neurons in rats exposed to a unilateral hypoxic-ischemic insult at 7 days of age. Animals were sacrificed at several time points after the injury, up to and including 7 days (Postnatal Day 14). Brain regions ipsilateral to the injury (inc...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7606
更新日期:2001-04-01 00:00:00
abstract::Urotensin-II (U-II) is a cyclic peptide identified recently in many mammalian species including man. U-II and its receptor are expressed in the central nervous system, in the cardiovascular system and in other peripheral tissues. Although this peptide has been reported initially to be a potent vasoconstrictor, increas...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.12.004
更新日期:2008-04-01 00:00:00
abstract::The effects of neonatal 6-hydroxydopamine (6-OHDA) treatment on the projection of locus coeruleus (LC) neurons to the dorsal part of the lateral geniculate nucleus (dLGN) were examined using histofluorescence and electrophysiological methods. Histofluorescence studies confirmed the previous results of Gustafson and Mo...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(91)90128-y
更新日期:1991-06-01 00:00:00
abstract::Embryonic stem cells (ESCs) promise an unlimited source of defined cells for cell transplantation therapy, while protocols for derivation of homogeneous populations of desirable cell types are yet to be developed and/or refined. Gamma aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervo...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2009.03.032
更新日期:2009-06-01 00:00:00
abstract::Increasing evidence indicates that the cytokines, tumor necrosis factor (TNF), interleukin-1, and/or interferon-gamma, may play a crucial role in the pathogenesis of multiple sclerosis. Several reports demonstrated that inhibition of TNF is highly protective in experimental allergic encephalomyelitis (EAE) when sensit...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(95)90044-6
更新日期:1995-02-01 00:00:00
abstract::Fish optic nerve sections were recently shown to be nonpermissive to growth of adult retinal axons. In addition, fish optic nerve myelin was found to inhibit growth of adult retinal axons and this inhibition was neutralized by IN-1 antibodies (known to block rat myelin-associated inhibitors). In this study we examined...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1994.1221
更新日期:1994-12-01 00:00:00