Abstract：
:In this review, we describe insights into beta-amyloid (Abeta) production using aged dogs as a model of human brain aging. The advantage of using dogs is that they naturally accumulate Abeta neuropathology with age. In parallel, dogs also develop age-associated learning and memory impairments. Thus, dogs can complement existing transgenic and nonhuman primate models typically used in aging studies. Dogs can live up to 18-19 years of age and companion dogs share the same environment as humans. Morphological brain changes as a function of age are clearly visible in vivo using magnetic image resonance scans. At the light microscopic level, dogs accumulate diffuse plaques with a distribution similar to that observed in human brain. Confocal studies suggest that Abeta accumulates on neuronal membranes in a segregated pattern. This pattern has been confirmed at the ultrastructural level using electron microscopy and provides insight into the deposition of Abeta into the extracellular space, possibly prior to overt plaque formation. Further, double immunogold labeling studies demonstrate that Abeta associated with the plasma membrane is colocalized with presenilin. These in vivo observations suggest a common site for both Abeta and presenilin supporting the hypothesis that the latter is involved with APP processing.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Head E,Torp Rdoi
10.1006/nbdi.2002.0476keywords:
subject
Has Abstractpub_date
2002-02-01 00:00:00pages
1-10issue
1eissn
0969-9961issn
1095-953Xpii
S0969996102904766journal_volume
9pub_type
杂志文章,评审abstract：:Aging is the strongest risk factor for metabolic, vascular and neurodegenerative diseases. Aging alone is associated with a gradual decline of cognitive and motor functions. Considering an increasing elderly population in the last century, understanding the cellular and molecular mechanisms contributing to brain aging...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2020.105008
更新日期：2020-09-01 00:00:00
abstract：:Human apolipoprotein E (apoE) exists in three isoforms: apoE2, apoE3 and apoE4. APOE ε4 is a major genetic risk factor for cardiovascular disease (CVD) and Alzheimer's disease (AD). ApoE mediates cholesterol metabolism by binding various receptors. The low-density lipoprotein receptor (LDLR) has a high affinity for ap...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.12.016
更新日期：2014-04-01 00:00:00
abstract：:Traumatic brain injury (TBI) leads to acute necrosis at the site of injury followed by a sequence of secondary events lasting from hours to weeks and often years. Targeting mitochondrial impairment following TBI has shown improvements in brain mitochondrial bioenergetics and neuronal function. Recently formoterol, a h...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2020.104866
更新日期：2020-07-01 00:00:00
abstract：:Here we report a gain in function for mutant (mt) superoxide dismutase I (SOD1), a cause of familial amyotrophic lateral sclerosis (FALS), wherein small soluble oligomers of mtSOD1 acquire a membrane toxicity. Phosphatidylglycerol (PG) lipid domains are selectively targeted, which could result in membrane damage or "t...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.03.014
更新日期：2018-07-01 00:00:00
abstract：:Transglutaminase 2 (TG2) is a multifunctional protein that modulates cell survival and death pathways. It is upregulated in numerous ischemic models, and protects primary neurons from oxygen and glucose deprivation. TG2 binds to the hypoxia inducible factor (HIF) 1beta and decreases the upregulation of hypoxic-induced...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2010.04.018
更新日期：2010-09-01 00:00:00
abstract：:β-Amyloid (Aβ) plaques in Alzheimer (AD) brains are surrounded by severe dendritic and axonal changes, including local spine loss, axonal swellings and distorted neurite trajectories. Whether and how plaques induce these neuropil abnormalities remains unknown. We tested the hypothesis that oligomeric assemblies of Aβ,...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.09.002
更新日期：2012-01-01 00:00:00
abstract：:An important aspect of Huntington's disease (HD) pathogenesis which may have important therapeutic implications is that the cellular events leading to cell death may be different in cortical and striatal neurons. In the present study, we characterized cellular changes in cortical and striatal neurons treated with the ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2003.09.013
更新日期：2004-02-01 00:00:00
abstract：:Inhibition of mitochondrial axonal trafficking by amyloid beta (Aβ) peptides has been implicated in early pathophysiology of Alzheimer's Disease (AD). Yet, it remains unclear whether the loss of motility inevitably induces the loss of mitochondrial function, and whether restoration of axonal trafficking represents a v...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.02.003
更新日期：2018-06-01 00:00:00
abstract：:Males and females show a different predisposition to certain types of seizures in clinical studies. Animal studies have provided growing evidence for sexual dimorphism of certain brain regions, including those that control seizures. Seizures are modulated by networks involving subcortical structures, including thalamu...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2014.05.010
更新日期：2014-12-01 00:00:00
abstract：:Giliosis is a hallmark of prion disease. A neurotoxic prion peptide (PrP106-126) induces astrocyte proliferation in the presence of microglia. This peptide also directly enhances microglial proliferation in culture. We have investigated this further to understand the method by which factors released by microglia and P...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1006/nbdi.1998.0169
更新日期：1998-04-01 00:00:00
abstract：:In the present study we analyze the molecular mechanisms underlying motor neuron degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene with a Gly(86) to Arg (G86R) mutation equivalent to that found in a subset of ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1006/nbdi.2000.0292
更新日期：2000-08-01 00:00:00
abstract：:TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, an...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2019.01.013
更新日期：2019-05-01 00:00:00
abstract：:The interest in the pedunculopontine tegmental nucleus (PPTg), a structure located in the brainstem at the level of the pontomesencephalic junction, has greatly increased in recent years because it is involved in the regulation of physiological functions that fail in Parkinson's disease and because it is a promising t...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2018.03.004
更新日期：2019-08-01 00:00:00
abstract：:Drugs that modify noradrenergic transmission such as atomoxetine and clonidine are increasingly prescribed for the treatment of attention deficit hyperactivity disorder (ADHD). However, the therapeutic targets of these compounds are unknown. Norepinephrine is also implicated in the hyperactivity exhibited by coloboma ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2006.05.007
更新日期：2006-09-01 00:00:00
abstract：:Peripherin is a type III intermediate filament protein normally undetectable in most brain neurons. Here, we report a similar pattern of peripherin expression in the brains of both mice treated with systemic injections of kainic acid (KA) and in peripherin transgenic mice (Per mice) over-expressing the normal peripher...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2004.10.009
更新日期：2005-03-01 00:00:00
abstract：:Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) belongs to a group of autosomal dominant neurodegenerative diseases, which are caused by the expansion of a polyglutamine repeat in the affected protein, in this case ataxin-3. Ataxin-3 is mainly localized in the cytoplasm; however, one hallmark of S...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2009.07.020
更新日期：2009-11-01 00:00:00
abstract：:Charcot-Marie-Tooth disease type 2B (CMT2B) is an inherited axonal peripheral neuropathy. It is characterised by prominent sensory loss, often complicated by severe ulcero-mutilations of toes or feet, and variable motor involvement. Missense mutations in RAB7A, the gene encoding the small GTPase Rab7, cause CMT2B and ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2014.01.021
更新日期：2014-05-01 00:00:00
abstract：BACKGROUND:Epidemiological studies suggest that the risk of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia is increased by prenatal exposure to viral or bacterial infection during pregnancy. It is still unclear how activation of the maternal immune response interacts with underlyi...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2019.01.025
更新日期：2019-05-01 00:00:00
abstract：:Familial amyotrophic lateral sclerosis (FALS) has been modeled in transgenic mice by introducing mutated versions of human genomic DNA encompassing the entire gene for Cu,Zn superoxide dismutase (SOD1). In this setting, the transgene is expressed throughout the body and results in mice that faithfully recapitulate man...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2005.06.005
更新日期：2005-12-01 00:00:00
abstract：:Parkinson's Disease (PD) and Multiple System Atrophy (MSA) are neurodegenerative diseases characterized neuropathologically by alpha-synuclein accumulation in brain cells. This accumulation is hypothesized to contribute to constitutive neuroinflammation, and to participate in the neurodegeneration. Cytokines, which ar...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2017.07.014
更新日期：2017-10-01 00:00:00
abstract：:Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 gene mutation in vascular smooth muscle cells (VSMCs), leading to ischemic stroke and vascular dementia. To date, the pathogenesis of CADASIL remains poorly understo...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2019.104561
更新日期：2019-12-01 00:00:00
abstract：:The noradrenergic nucleus Locus Coeruleus (LC) densely innervates limbic structures. In rats, the damage to LC by the neurotoxin DSP-4, converts episodic limbic seizures induced by bicuculline infusion in the anterior piriform cortex (APC) into self-sustaining status epilepticus (SE). SE induced by this approach is si...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2008.02.008
更新日期：2008-06-01 00:00:00
abstract：:Huntington's disease (HD) is a progressive neurodegenerative genetic disorder which leads to motor, cognitive and psychiatric disturbances. The primary neuropathological hallmark is atrophy of the striatum. Cannabinoid CB1 receptors (CB1Rs) are particularly enriched in the striatum and previous works indicate their ea...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.03.006
更新日期：2011-06-01 00:00:00
abstract：:Experiments reported here were motivated by studies in both human epilepsy and animal models in which stunted dendritic arbors are observed. Our goal was to determine if chronic network hyperexcitability alters dendritic growth. Experiments were conducted in hippocampal slice cultures obtained from infant mice that ex...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2007.08.018
更新日期：2008-02-01 00:00:00
abstract：:Matrix metalloproteinases (MMPs) are involved in tissue repair, cell death and morphogenesis. We investigated the role of the gelatinases MMP-2 and MMP-9 in the pathogenesis of neuronal death induced by prolonged seizures in the developing brain. Seven-day-old rats, MMP-9 knockout mice and transgenic rats overexpressi...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2012.06.023
更新日期：2012-12-01 00:00:00
abstract：:The dysregulation of glycogen synthase kinase-3 (GSK3) has been implicated in Alzheimer disease (AD) pathogenesis and in Abeta-induced neurotoxicity, leading us to investigate it as a therapeutic target in an intracerebroventricular Abeta infusion model. Infusion of a specific GSK3 inhibitor SB216763 (SB) reduced a do...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2008.10.007
更新日期：2009-02-01 00:00:00
abstract：:It is widely accepted that the loss of function of different cellular proteins following their aggregation into highly stable aggregates or the gain of pathologic function of the resulting macromolecular assemblies or both processes are tightly associated to distinct debilitating neurodegenerative diseases such as Alz...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2017.03.011
更新日期：2018-01-01 00:00:00
abstract：:Neural transplantation has been investigated experimentally and clinically for the purpose of developing new treatment options for intractable epilepsy. In the present study we assessed the anticonvulsant efficacy and safety of bilateral allotransplantation of genetically engineered striatal GABAergic rat cell lines i...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2008.05.010
更新日期：2008-09-01 00:00:00
abstract：:3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase that has been used to explore the primary mechanisms of cell death associated with mitochondrial dysfunction and neurodegeneration in Huntington's disease. In this study we investigated the ability of brain-derived neurotrophic factor...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2009.06.006
更新日期：2009-09-01 00:00:00
abstract：:In the injured central nervous system (CNS), transforming growth factor (TGF)-β1/2-induced scarring and wound cavitation impede axon regeneration implying that a combination of both scar suppression and axogenic treatments is required to achieve functional recovery. After treating acute and chronic dorsal funicular sp...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.12.008
更新日期：2014-04-01 00:00:00
