Abstract：
:There are multiple lines of evidence showing that oxidative stress and aberrant mitogenic signaling play an important role in the pathogenesis of Alzheimer disease. However, the chronological relationship between these and other events associated with disease pathogenesis is not known. Given the important role that mitogen-activated protein kinase (MAPK) pathways play in both mitogenic signaling (ERK) and cellular stress signaling (JNK/SAPK and p38), we investigated the chronological and spatial relationship between activated ERK, JNK/SAPK and p38 during disease progression. While all three kinases are activated in the same susceptible neurons in mild and severe cases (Braak stages III-VI), in non-demented cases with limited pathology (Braak stages I and II), both ERK and JNK/SAPK are activated but p38 is not. However, in non-demented cases lacking any sign of pathology (Braak stage 0), either ERK alone or JNK/SAPK alone can be activated. Taken together, these findings indicate that MAPK pathways are differentially activated during the course of Alzheimer disease and, by inference, suggest that both oxidative stress and abnormalities in mitotic signaling can independently serve to initiate, but both are necessary to propagate, disease pathogenesis. Therefore, we propose that both 'hits', oxidative stress and mitotic alterations, are necessary for the progression of Alzheimer disease.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Zhu X,Castellani RJ,Takeda A,Nunomura A,Atwood CS,Perry G,Smith MAdoi
10.1016/s0047-6374(01)00342-6subject
Has Abstractpub_date
2001-12-01 00:00:00pages
39-46issue
1eissn
0047-6374issn
1872-6216pii
S0047-6374(01)00342-6journal_volume
123pub_type
杂志文章abstract：:The tumor suppressors p16(INK4a) and p53 have been implicated as contributors to age-associated stem cell decline. Key functions of p53 are the induction of cell cycle arrest, senescence, or apoptosis in response to DNA damage. Here, we examine senescence, apoptosis, and DNA damage responses in a mouse accelerated agi...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2009.01.001
更新日期：2009-04-01 00:00:00
abstract：:To gain insight into the anti-ageing mechanisms of caloric restriction (CR), liver mitochondria were isolated from male Brown-Norway rats of different ages (fully fed control and CR) and various specific markers of non-enzymatic protein modification (by oxidative, glyco- and lipoxidative-reactions) were measured by GC...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2004.06.002
更新日期：2004-08-01 00:00:00
abstract：:Longevity regulatory genes include the Forkhead transcription factor FOXO, in addition to NAD-dependent histone deacetylase silent information regulator 2 (Sir2). The FOXO/DAF-16 family of transcription factors constitute an evolutionarily conserved subgroup within a larger family known as winged helix or Forkhead tra...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2004.09.021
更新日期：2005-01-01 00:00:00
abstract：:Hypertension is a main risk factor for cerebrovascular disease, including vascular dementia. The present study was designed to evaluate if hypertension-dependent changes of the hippocampus of spontaneously hypertensive rats (SHR) of different ages were related with those occurring in vascular dementia. The hippocampus...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(01)00362-1
更新日期：2002-03-15 00:00:00
abstract：:The localization of the beta/A4 amyloid precursor protein (APP) was studied in the human lumbar paravertebral sympathetic ganglia of subjects of different ages, free of neurologic disease, using combined immunohistochemistry and image analysis techniques (optic microdensitometry). To ascertain which cells displayed AP...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(94)91588-1
更新日期：1994-10-20 00:00:00
abstract：:Glucocorticoids promote the development of many organs including intestine. At the cellular level, the activity of glucocorticoids is regulated by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) which converts active glucocorticoids to inactive metabolites. As 11 beta HSD is also expressed in the intestine, this en...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(97)00079-1
更新日期：1997-11-01 00:00:00
abstract：:Quantitative measurements of glycogen in aging bruchids showed there was a considerable decrease (> 50%) with age except on the fifth day when an increase was observed, followed by a decrease on the sixth day. The variations in glycogen content with age suggests that glycogen serves as one of the energy sources respon...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(80)90082-2
更新日期：1980-01-01 00:00:00
abstract：:Experimental studies have not shown that the 'common' clinical experience, which suggests that wound healing is impaired in an old organism, is valid for healthy old experimental animals. We have developed a model in the rat for ischemic wound healing by using an H-shaped double skin flap, where the test wound is the ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(91)90094-g
更新日期：1991-05-01 00:00:00
abstract：:The effects of age and chronic propranolol treatment on the agonist-induced rise in intracellular free Ca2+ ([Ca2+]i), an index for the coupling of receptor-second messenger generation, was studied using a dispersed rat submandibular gland preparation. Muscarinic stimulation (10 microns carbachol) caused a rapid (T1/2...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(91)90005-k
更新日期：1991-11-15 00:00:00
abstract：:Anucleate minicells produced by a mutated strain of Escherichia coli remain metabolically active for up to 48 h at 37 degrees C. Minicells of increasing age have been infected with the coliphage T7. Infection results in the onset of transcription and translation producing T7 encoded polypeptides. Quantitative and qual...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(84)90045-9
更新日期：1984-10-15 00:00:00
abstract：:To test the validity of estimating age-related changes in rat liver nuclear RNA synthesis by following the incorporation of radioactive nucleotides into an acid-insoluble product, age-related changes in endogenous nucleotide concentration were investigated. Both the total nucleotide and the nucleoside monophosphate (N...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(80)90087-1
更新日期：1980-02-01 00:00:00
abstract：:Human diploid fibroblasts, TIG-1, were serially subcultivated at low inoculation densities thus maintaining the cultures in log phase throughout their in vitro lifespan. Their lifespan was shortened in calendar time without decreasing the cumulative number of population doublings when compared with the lifespan of cel...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(80)90034-2
更新日期：1980-07-01 00:00:00
abstract：:Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual lo...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2004.07.012
更新日期：2005-03-01 00:00:00
abstract：:Mice with an overall deletion of the sensory neuropeptide α-calcitonin gene-related peptide (α-CGRP) develop an age-dependent osteopenic bone phenotype. Underlying molecular mechanisms of how αCGRP affects bone cell metabolism are not well understood. This study aims to characterize differences in metabolic parameters...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2020.111265
更新日期：2020-07-01 00:00:00
abstract：:The risk for developing colorectal cancer increases exponentially with age. We demonstrate that spontaneous loss of folate in the colon results in DNA damage accumulation and aberrant DNA damage responses that may contribute to the increased genomic instability and cancer risk in colon. We find greater than 2-fold cha...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2012.01.003
更新日期：2012-02-01 00:00:00
abstract：:The response of the rat isolated testicular capsule to norepinephrine (NE), acetylcholine (ACh) and prostaglandins (PG) was found to be age-dependent. The testicular capsular contractions attributable to smooth muscle cells located within the tunica albuginea may be involved in the transport of non-motile spermatozoa ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(79)90015-0
更新日期：1979-12-01 00:00:00
abstract：:Both vascular relaxation and cAMP accumulation mediated by beta adrenergic agonists declines with increasing age. We have developed a method to measure the biologically relevant cAMP bound to the regulatory subunits of cAMP-dependent protein kinase in rat aorta. In homogenates of rat aorta, binding of [3H]cAMP was sat...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(90)90064-m
更新日期：1990-04-09 00:00:00
abstract：:This paper is part of a series aimed to investigate the mechanism of the action of Folcysteine, a substance that has the capacity to release in the body active -SH groups and has been proved to be effective in the control of menopausal troubles. As an experimental model the ovariectomized rat, rather similar, from the...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(75)90043-3
更新日期：1975-09-01 00:00:00
abstract：:We have developed a cell model for loss of differentiated gene expression in cellular aging. Over long periods in culture, bovine adrenocortical cells lose expression of a specialized gene, steroid 17 alpha-hydroxylase. The decline in expression of 17 alpha-hydroxylase in mass cultures and clones of bovine adrenocorti...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(91)90115-g
更新日期：1991-04-01 00:00:00
abstract：:The purpose of this research is to determine possible causes and mechanisms involved in the age-associated decline in mitochondrial activity. We have focused on cytochrome c oxidase because it is comprised of both nuclear and mitochondrial-encoded subunits and may provide some insight into the coordination of the two ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(98)00043-8
更新日期：1998-06-15 00:00:00
abstract：:On a DNA basis, there is higher concentration of polysomes in the brain of newborn than in the brain of adult mice, but there is no maturation-dependent decrease in tRNA content during postnatal development. The amino acid incorporating activity of cell-free systems with polysomes or mitochondria from newborn brain ex...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(79)90040-x
更新日期：1979-05-01 00:00:00
abstract：:In this paper we examined the impact of age on cognitive functions and the age-related modifications of egr1 expression, an inducible transcription factor with a confirmed role in synaptic plasticity and regulation of the proteasome activity, on pet dogs. Additionally, we examined the age-related changes of some eleme...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2009.01.007
更新日期：2009-05-01 00:00:00
abstract：:In the present study, a number of physiological and behavioral measures that are related to metabolism were continuously monitored in 19-month-old male Fischer 344 rats that were fed ad libitum or fed a caloric restricted diet. Caloric restricted rats ate fewer meals but consumed more food during each meal and spent m...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/0047-6374(89)90044-4
更新日期：1989-05-01 00:00:00
abstract：:We have developed a novel method to examine the translational fidelity of mammalian ribosomes in vitro, where protamine mRNA was used as a template. This method enabled us to determine frequency of misrecognition of purine bases at the second position of arginine codons (AGR/AAR) in the mRNA. Using this method the fid...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(83)90002-7
更新日期：1983-05-01 00:00:00
abstract：:Atypical bodies (ABs), related to aging, are described in the central nervous system of normal aged hamsters. Our study used ultrastructural microscopy and quantitative stereology analysis to study these structures in the hypothalamus and brain stem of 3, 6, 12, 18, 24 and 30 month-old hamsters. We found that these co...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(96)01755-1
更新日期：1996-09-09 00:00:00
abstract：:As a prerequisite to investigating the specification and differentiation of cardiac tissue in vitro, the ontogeny of a number of putative cardiac-specific, and striated muscle-specific gene transcripts has been studied. The probes used include cDNAs of alpha-actins, myosin heavy chains, myosin light chains, alpha-trop...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(94)90019-1
更新日期：1994-12-16 00:00:00
abstract：:Hematopoietic stem cell performance and identity, crucial for homeostasis of the blood-forming system, is governed by extrinsic factors found in the bone marrow microenvironment. Communication within hematopoietic stem cell niches occurs via soluble factors or cell-to-cell contacts between niche and blood-forming cell...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2020.111329
更新日期：2020-10-01 00:00:00
abstract：:The incidence of chronic diseases such as cardiovascular diseases is lower in Mediterranean Southern Europe than Northern Europe. This may be due to a lower level of oxidative stress and a higher antioxidant status in people living around the Mediterranean Sea. Oxidative stress may influence the rate of shortening of ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2012.04.003
更新日期：2012-06-01 00:00:00
abstract：:Selenium (Se) is an essential trace mineral mediating its biological function primarily through selenoproteins. Accumulated lines of evidence indicate important roles of selenoproteins in the maintenance of optimal brain functions via redox regulation. Decreased expression of several selenoproteins is associated with ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2010.02.006
更新日期：2010-04-01 00:00:00
abstract：:The functional deterioration of an organism with age causes the major problem of maintaining the quality of life at old age. Degenerative changes in the organism may to some extent reflect alterations that can be observed in cells during in vitro replicative senescence. At the cellular level, the receptor-mediated end...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/s0047-6374(02)00029-5
更新日期：2002-04-30 00:00:00
