Abstract：
:Accumulation of disease-related proteins is a characteristic event observed in the pathogenesis of neurodegenerative diseases. β-secretase (BACE)-1, which initiates generation of β-amyloid (Aβ), is increased in the Alzheimer's diseased brain. However, the mechanisms of BACE1 accumulation in Alzheimer's disease are largely unknown. In this report, we found that small ubiquitin-like modifier (SUMO)-1 interacts with the dileucine motif of BACE1 and regulates the level of BACE1 protein. This was proved by the coimmunoprecipitation, and gain or loss of function experiments. Altering 3 SUMO isoforms affects BACE1 protein levels, and consequently results in altered amyloid precursor protein processing and Aβ generation. BACE1 levels were increased in response to Aβ or apoptosis, but not in cells lacking SUMO1. Aβ increased SUMO1 protein levels in rat cortical neurons. Moreover, SUMO1 immunoreactivity was increased in the amyloid precursor protein transgenic mice. Furthermore, the C-terminus fragments of BACE1 containing dileucine motif reduced Aβ generation by SUMO1 overexpression. Our study indicates SUMO1 is not only a novel and potent regulator of BACE1 accumulation and Aβ generation but also a potential therapeutic target for Alzheimer's disease.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Yun SM,Cho SJ,Song JC,Song SY,Jo SA,Jo C,Yoon K,Tanzi RE,Choi EJ,Koh YHdoi
10.1016/j.neurobiolaging.2012.08.005subject
Has Abstractpub_date
2013-03-01 00:00:00pages
650-62issue
3eissn
0197-4580issn
1558-1497pii
S0197-4580(12)00427-7journal_volume
34pub_type
杂志文章abstract：:Threshold and suprathreshold sensitivities to 13 bitter compounds were determined for 16 young adults (mean age = 27.4 years) and 18 elderly persons (mean age = 81.3 years). Half of the subjects in each age group were tasters of the bitter compound phenylthiocarbamide (PTC) and half were nontasters. Both detection and...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(94)90057-4
更新日期：1994-11-01 00:00:00
abstract：:Glycogen synthase kinase-3β (GSK3B) and cyclin-dependent kinase 5 (CDK5) are the 2 major protein kinases involved in abnormal phosphorylation of tau. To determine their potential role in the pathogenesis of Parkinson's disease (PD) we analyzed 2 functional single nucleotide polymorphisms (SNPs) of GSK3B (rs334558 and ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.10.016
更新日期：2012-07-01 00:00:00
abstract：:In Alzheimer's disease (AD), amyloid-β (Aβ) deposits accumulate in the brain parenchyma and contain fibrils of aggregated heterogeneous Aβ peptides. In addition to fibrils, Aβ aggregates into stable soluble species (termed Aβ oligomers), which are increasingly viewed as the key drivers of early neurodegenerative event...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.05.023
更新日期：2014-11-01 00:00:00
abstract：:The G4C2 hexanucleotide repeat expansion, located in the first intron of the C9ORF72 gene, represents a major genetic hallmark of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Several hypotheses have been proposed on how the transcribed repeat RNA leads to the development of amyotrophic lateral ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.09.012
更新日期：2015-02-01 00:00:00
abstract：:Cell culture systems for evaluating the biological effects of the beta-amyloid protein are potentially important tools in the study of the pathogenesis of Alzheimer's disease. In this report, methodological considerations in the assessment of beta-amyloid neurotoxicity are discussed. Chronic incubation of beta 1-40 in...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/0197-4580(92)90065-6
更新日期：1992-09-01 00:00:00
abstract：:We studied the hippocampal angle and spatial relationships of medial temporal lobe (MTL) structures, using midbrain colliculi and inter-collicular sulcus (ICS) as landmarks, and measured MTL width on axial 3D-T1-weighted MRI at ICS level in 41 normal, aged participants. Mean hippocampal angle was 29 degrees (range 17-...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(02)00013-1
更新日期：2003-01-01 00:00:00
abstract：:Parkinson's disease (PD) is a progressive neurodegenerative disease with typical motor symptoms due to the preferential loss of midbrain dopaminergic (mDA) neurons in the Substantia nigra pars compacta. Several proteins of the homeodomain family are crucial for the development of mDA neurons. These proteins remain exp...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.08.014
更新日期：2009-05-01 00:00:00
abstract：:Omegaconotoxin binding was studied in young (3 months) and old (24 months) male Sprague-Dawley rats. In both groups omegaconotoxin binding displayed high affinity, was specific and saturable. The age-related changes are mainly a decrease in the Bmax in striatum and cortex (-29% and -31%, respectively). Binding paramet...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(90)90010-w
更新日期：1990-07-01 00:00:00
abstract：:Vascular risk factors (VRFs) increase the risk of Alzheimer's disease (AD) and contribute to neurodegenerative processes. The purpose of this study was to investigate whether increasing number of VRFs contributes to within-cohort differences in cortical thickness (CThk) among adults with mild cognitive impairment (MCI...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.05.011
更新日期：2016-09-01 00:00:00
abstract：:Genetic factors have been suggested to be involved in the pathogenesis of sporadic inclusion body myositis (sIBM). Sequestosome 1 (SQSTM1) and valosin-containing protein (VCP) are 2 key genes associated with several neurodegenerative disorders but have yet to be thoroughly investigated in sIBM. A candidate gene analys...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.07.024
更新日期：2016-11-01 00:00:00
abstract：:Here we report the relationship between age at onset, clinical course and genotype in a family with combined LRRK2 G2019S and Parkin exon 2 deletions. In the combined mutation carriers the age at onset and clinical course was highly variable and not always younger than in the carriers of LRRK2 G2019S mutations alone. ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.05.030
更新日期：2010-04-01 00:00:00
abstract：:Distortions in the rest-activity rhythm in aging are commonly observed. Neurodegenerative changes of the suprachiasmatic nucleus have been proposed to underlie this disrupted rhythm. However, based on previous studies, it can be proposed that white matter hyperintensities (WMH) may also play a role in the altered rest...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.02.014
更新日期：2008-08-01 00:00:00
abstract：:We have assessed the frequency of alpha-synuclein (SNCA) mutations in Japanese patients with familial or sporadic Parkinson's disease (PD) and surveyed their associated clinical manifestations. We screened SNCA exon 3 in 988 patients without SNCA multiplications (430 with autosomal dominant PD and 558 with sporadic PD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.05.022
更新日期：2017-09-01 00:00:00
abstract：:The performance of male A/J and C57BL/6J mice from three age groups (4, 18, and 24 months) was observed in a battery of tests designed to assess age-related impairments in motor abilities. A/J mice were superior to C57BL/6J mice in tasks requiring upper body strength, such as tests of grip strength and tightrope perfo...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(81)90025-7
更新日期：1981-10-01 00:00:00
abstract：:Neuroimage measures from magnetic resonance (MR) imaging, such as cortical thickness, have been playing an increasingly important role in searching for biomarkers of Alzheimer's disease (AD). Recent studies show that, AD, mild cognitive impairment (MCI) and normal control (NC) can be distinguished with relatively high...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.11.008
更新日期：2012-02-01 00:00:00
abstract：:Apolipoprotein E (APOE) alleles are associated with longevity in genome-wide scans, with ε4 correlated with shorter life, and ε2 with longer life, than ε3. We hypothesized that rare APOE variants with large individual effects might also contribute to long-term good health. The APOE exons and promoter were resequenced ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.09.010
更新日期：2014-03-01 00:00:00
abstract：:Aging-related episodic memory decline is often attributed to insufficient encoding of new information, although the underlying neural processes remain elusive. We here tested the hypothesis that impaired memory consolidation contributes to aging-related memory decline. To this end, we used resting state functional mag...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.06.004
更新日期：2016-09-01 00:00:00
abstract：:Studies in asymptomatic granulin gene (GRN) mutation carriers are essential to improve our understanding of the pattern and timing of early morphologic brain changes in frontotemporal lobar degeneration. The main objectives of this study were to assess the effect of age in cortical thickness changes (CTh) in preclinic...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.11.005
更新日期：2013-05-01 00:00:00
abstract：:An extensive literature reports changes in quantitative electroencephalogram (QEEG) with aging and a relationship between magnitude of changes and degree of clinical deterioration in progressive dementia. Longitudinal studies have demonstrated QEEG differences between mild cognitively impaired (MCI) elderly who go on ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.07.021
更新日期：2006-03-01 00:00:00
abstract：:The progressive dysfunction and loss of neurons in Alzheimer's disease (AD) is accompanied by marked structural changes in innumerable neuronal cell bodies and neurites, particularly in limbic and association cortices. Qualitatively indistinguishable neuronal lesions occur in much smaller numbers during normal aging. ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/0197-4580(86)90055-2
更新日期：1986-11-01 00:00:00
abstract：:Dualistic effects of acetylcholine-esterase inhibitors on neuronal as well as vasoregulative function have been debated. This study investigated for the first time effects of medication on both components. Visually evoked potentials and resultant hemodynamic responses were assessed in Alzheimer patients (n=31) without...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.02.017
更新日期：2009-12-01 00:00:00
abstract：:The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzh...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2017.03.001
更新日期：2017-08-01 00:00:00
abstract：:Flexible instrumental learning is required to harness the appropriate behaviors to obtain rewards and to avoid punishments. The precise contribution of dopaminergic midbrain regions (substantia nigra/ventral tegmental area [SN/VTA]) to this form of behavioral adaptation remains unclear. Normal aging is associated with...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.03.030
更新日期：2013-10-01 00:00:00
abstract：:Cholesterol is implicated in the development of late-onset Alzheimer's disease (AD). We sought to determine the associations between beta amyloid (Aβ) plaque deposition in vivo using Pittsburgh compound B (PiB) and several indices of cholesterol homeostasis (i.e., total cholesterol, high-density lipoprotein cholestero...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.09.040
更新日期：2014-04-01 00:00:00
abstract：:In the rhesus monkey primary visual cortex, there are bundles of vertically oriented myelinated axons, which mainly contain efferent fibers originating from pyramidal cells. At the level of layer 4Cbeta, the bundles are regularly arranged and the nerve fibers in them are closely packed. In order to determine if a sign...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00169-x
更新日期：2000-09-01 00:00:00
abstract：:Age-related macular degeneration (AMD) has been linked to memory deficits, with no established neural mechanisms. We collected resting-state brain functional magnetic resonance imaging and standardized verbal recall tests from 42 older adults with AMD and 41 age-matched controls. We used seed-based whole brain analysi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.07.020
更新日期：2020-11-01 00:00:00
abstract：:Striatal degeneration may contribute to cognitive impairment in older people. Here, we examine the relation of degeneration of the striatum and substructures to cognitive decline and dementia in subjects with a wide range of cognitive function. Data are from the prospective community-based Honolulu Asia Aging Study of...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.09.027
更新日期：2012-02-01 00:00:00
abstract：:Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidatio...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.03.005
更新日期：2016-07-01 00:00:00
abstract：:Young, middle-aged, old, and senescent Fischer 344 x Brown Norway F1 hybrid rats were trained in either the trace or delay eyeblink conditioning task in order to investigate how aging affects associative learning and memory over the life span. Senescent rats at 34-35 months showed severe impairments in acquisition of ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00194-9
更新日期：2001-01-01 00:00:00
abstract：:Although important in neurodegeneration, systematic studies of nicotinic acetylcholine receptor expression in normal aging human brains are difficult to perform. We have studied the expression of nicotinic receptor alpha 4-1 and alpha 5 mRNA in the frontal and parietal isocortex of 3- (young adult), 24- (late middle a...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)80316-8
更新日期：1997-05-01 00:00:00
