Familial Alzheimer's Disease Lymphocytes Respond Differently Than Sporadic Cells to Oxidative Stress: Upregulated p53-p21 Signaling Linked with Presenilin 1 Mutants.

Abstract:

:Familial (FAD) and sporadic (SAD) Alzheimer's disease do not share all pathomechanisms, but knowledge on their molecular differences is limited. We previously reported that cell cycle control distinguishes lymphocytes from SAD and FAD patients. Significant differences were found in p21 levels of SAD compared to FAD lymphocytes. Since p21 can also regulate apoptosis, the aim of this study was to compare the response of FAD and SAD lymphocytes to oxidative stress like 2-deoxy-D-ribose (2dRib) treatment and to investigate the role of p21 levels in this response. We report that FAD cells bearing seven different PS1 mutations are more resistant to 2dRib-induced cell death than control or SAD cells: FAD cells showed a lower apoptosis rate and a lower depolarization of the mitochondrial membrane. Despite that basal p21 cellular content was lower in FAD than in SAD cells, in response to 2dRib, p21 mRNA and protein levels significantly increased in FAD cells. Moreover, we found a higher cytosolic accumulation of p21 in FAD cells. The transcriptional activation of p21 was shown to be dependent on p53, as it can be blocked by PFT-α, and correlated with the increased phosphorylation of p53 at Serine 15. Our results suggest that in FAD lymphocytes, the p53-mediated increase in p21 transcription, together with a shift in the nucleocytoplasmic localization of p21, confers a survival advantage against 2dRib-induced apoptosis. This compensatory mechanism is absent in SAD cells. Thus, therapeutic and diagnostic designs should take into account possible differential apoptotic responses in SAD versus FAD cells.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Wojsiat J,Laskowska-Kaszub K,Alquézar C,Białopiotrowicz E,Esteras N,Zdioruk M,Martin-Requero A,Wojda U

doi

10.1007/s12035-016-0105-y

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

5683-5698

issue

7

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-016-0105-y

journal_volume

54

pub_type

杂志文章
  • The Dynamics of Impaired Blood-Brain Barrier Restoration in a Rat Model of Co-morbid Injury.

    abstract::Defect in brain microperfusion is increasingly recognized as an antecedent event to Alzheimer's disease (AD) and ischemia. Nevertheless, studies on the role of impaired microperfusion as a pathological trigger to neuroinflammation, Aβ deposition as well as blood-brain barrier (BBB) disruption, and the etiological link...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-0904-4

    authors: Amtul Z,Yang J,Nikolova S,Lee TY,Bartha R,Cechetto DF

    更新日期:2018-10-01 00:00:00

  • Disrupted Excitatory Synaptic Contacts and Altered Neuronal Network Activity Underpins the Neurological Phenotype in PCDH19-Clustering Epilepsy (PCDH19-CE).

    abstract::PCDH19-Clustering Epilepsy (PCDH19-CE) is an infantile onset disorder caused by mutation of the X-linked PCDH19 gene. Intriguingly, heterozygous females are affected while hemizygous males are not. While there is compelling evidence that this disorder stems from the coexistence of WT and PCDH19-null cells, the cellula...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02242-4

    authors: Mincheva-Tasheva S,Nieto Guil AF,Homan CC,Gecz J,Thomas PQ

    更新日期:2021-01-07 00:00:00

  • Knock-in of Mutated hTAU Causes Insulin Resistance, Inflammation and Proteostasis Disturbance in a Mouse Model of Frontotemporal Dementia.

    abstract::Diabetes and obesity have been implicated as risk factors for dementia. However, metabolic mechanisms and associated signalling pathways have not been investigated in detail in frontotemporal dementia. We therefore here characterised physiological, behavioural and molecular phenotypes of 3- and 8-month-old male tau kn...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-019-01722-6

    authors: Hull C,Dekeryte R,Koss DJ,Crouch B,Buchanan H,Delibegovic M,Platt B

    更新日期:2020-01-01 00:00:00

  • Dcf1 Triggers Dendritic Spine Formation and Facilitates Memory Acquisition.

    abstract::Dendritic spines, a special kind of structure in nerve cells, play a key role in performing cellular function. Structural abnormalities of the dendritic spine may contribute to synaptic dysfunction and have been implicated in memory formation. However, the molecular mechanisms that trigger dendritic spine loss remain ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0349-6

    authors: Liu Q,Feng R,Chen Y,Luo G,Yan H,Chen L,Lin R,Ding Y,Wen T

    更新日期:2018-01-01 00:00:00

  • The Microbiota-Gut-Immune-Glia (MGIG) Axis in Major Depression.

    abstract::There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons, orchestrate various neuromodula...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-020-01961-y

    authors: Rudzki L,Maes M

    更新日期:2020-10-01 00:00:00

  • Chromophore-Assisted Light Inactivation of the V-ATPase V0c Subunit Inhibits Neurotransmitter Release Downstream of Synaptic Vesicle Acidification.

    abstract::Synaptic vesicle proton V-ATPase is an essential component in synaptic vesicle function. Active acidification of synaptic vesicles, triggered by the V-ATPase, is necessary for neurotransmitter storage. Independently from its proton transport activity, an additional important function of the membrane-embedded sector of...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1324-1

    authors: Rama S,Boumedine-Guignon N,Sangiardi M,Youssouf F,Maulet Y,Lévêque C,Belghazi M,Seagar M,Debanne D,El Far O

    更新日期:2019-05-01 00:00:00

  • Characteristic CSF prion seeding efficiency in humans with prion diseases.

    abstract::The development of in vitro amplification systems allows detecting femtomolar amounts of prion protein scrapie (PrP(Sc)) in human cerebrospinal fluid (CSF). We performed a CSF study to determine the effects of prion disease type, codon 129 genotype, PrP(Sc) type, and other disease-related factors on the real-time quak...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8709-6

    authors: Cramm M,Schmitz M,Karch A,Zafar S,Varges D,Mitrova E,Schroeder B,Raeber A,Kuhn F,Zerr I

    更新日期:2015-02-01 00:00:00

  • Rapid Regulation of Depression-Associated Genes in a New Mouse Model Mimicking Interferon-α-Related Depression in Hepatitis C Virus Infection.

    abstract::Major depression is a serious side effect of interferon-α (IFN-α), which is used in the therapy of hepatitis C virus (HCV) infection. Due to the lack of reproducible animal models, the mechanisms underlying IFN-α-related depression are largely unknown. We herein established a mouse model, in which murine IFN-α (250 IU...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8861-z

    authors: Hoyo-Becerra C,Liu Z,Yao J,Kaltwasser B,Gerken G,Hermann DM,Schlaak JF

    更新日期:2015-08-01 00:00:00

  • Prognostic Value of YKL-40 in Patients with Glioblastoma: a Systematic Review and Meta-analysis.

    abstract::YKL-40 is the most highly expressed gene in glioblastoma compared with normal brain tissues. Previous studies assessing the association between YKL-40 and survival in glioblastoma patients reported varying magnitude of estimates. The objective of this meta-analysis was to determine the prognostic value of YKL-40 in gl...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,meta分析,评审

    doi:10.1007/s12035-016-9878-2

    authors: Qin G,Li X,Chen Z,Liao G,Su Y,Chen Y,Zhang W

    更新日期:2017-07-01 00:00:00

  • Plasmalogens Inhibit Endocytosis of Toll-like Receptor 4 to Attenuate the Inflammatory Signal in Microglial Cells.

    abstract::Microglial activation is a pathological feature of many neurodegenerative diseases and the role of cellular lipids in these diseases is mostly unknown. It was known that the special ether lipid plasmalogens (Pls) were reduced in the brain and blood samples of Alzheimer's disease (AD) patients. It has recently been rep...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1307-2

    authors: Ali F,Hossain MS,Sejimo S,Akashi K

    更新日期:2019-05-01 00:00:00

  • Olfactory Deprivation Hastens Alzheimer-Like Pathologies in a Human Tau-Overexpressed Mouse Model via Activation of cdk5.

    abstract::Olfactory dysfunction is a recognized risk factor for the pathogenesis of Alzheimer's disease (AD), while the mechanisms are still not clear. Here, we applied bilateral olfactory bulbectomy (OBX), an olfactory deprivation surgery to cause permanent anosmia, in human tau-overexpressed mice (htau mice) to investigate ch...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-9007-z

    authors: Li K,Liu FF,He CX,Huang HZ,Xie AJ,Hu F,Liu D,Wang JZ,Zhu LQ

    更新日期:2016-01-01 00:00:00

  • Involvement of Claudin-11 in Disruption of Blood-Brain, -Spinal Cord, and -Arachnoid Barriers in Multiple Sclerosis.

    abstract::It is important to understand the molecular mechanisms of barrier disruption in the central nervous system (CNS) of patients with multiple sclerosis (MS). The purpose of the present study was to clarify whether claudin-11 is involved in the disruption of two endothelial barriers (blood-brain barrier (BBB) and blood-sp...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1207-5

    authors: Uchida Y,Sumiya T,Tachikawa M,Yamakawa T,Murata S,Yagi Y,Sato K,Stephan A,Ito K,Ohtsuki S,Couraud PO,Suzuki T,Terasaki T

    更新日期:2019-03-01 00:00:00

  • Legumain Knockout Protects Against Aβ1-42-Induced AD-like Cognitive Deficits and Synaptic Plasticity Dysfunction Via Inhibiting Neuroinflammation Without Cleaving APP.

    abstract::Neuroinflammation is the important pathological feature of Alzheimer's disease (AD). Legumain, a lysosomal cysteine protease, plays an important role in neuroinflammation during ischemic stroke and depressive disorder. Legumain is involved in AD process through cleaving APP; however, it is unclear if legumain can poss...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02219-3

    authors: Chen R,Zhang Q,Yan Y,Zhang Y,Zhang T

    更新日期:2020-11-21 00:00:00

  • Membrane biophysics and mechanics in Alzheimer's disease.

    abstract::Alzheimer's disease is a chronic neurodegenerative disorder characterized by neuronal loss, cerebrovascular inflammation, and accumulation of senile plaques in the brain parenchyma and cerebral blood vessels. Amyloid-beta peptide (Abeta), a major component of senile plaques, has been shown to exert multiple toxic effe...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-010-8121-9

    authors: Yang X,Askarova S,Lee JC

    更新日期:2010-06-01 00:00:00

  • p38 MAPK Participates in the Mediation of GLT-1 Up-regulation During the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning.

    abstract::Our previous study has proved that the up-regulation of glial glutamate transporter 1 (GLT-1) played an important role in the acquisition of brain ischemic tolerance after cerebral ischemic preconditioning (CIP) in rats. However, little is known about the mechanism involved in the up-regulation of GLT-1 in the process...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9652-x

    authors: Zhang M,Gong JX,Wang JL,Jiang MY,Li L,Hu YY,Qi J,Zhang LY,Zhao H,Cui X,Xian XH,Li WB

    更新日期:2017-01-01 00:00:00

  • Amyloid-β Oligomers Regulate ADAM10 Synaptic Localization Through Aberrant Plasticity Phenomena.

    abstract::A disintegrin and metalloproteinase 10 (ADAM10) is a synaptic enzyme that has been previously shown to limit amyloid-β1-42 (Aβ1-42) peptide formation in Alzheimer's disease (AD). Furthermore, ADAM10 participates to spine shaping through the cleavage of adhesion molecules and its activity is under the control of synapt...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-019-1583-5

    authors: Marcello E,Musardo S,Vandermeulen L,Pelucchi S,Gardoni F,Santo N,Antonucci F,Di Luca M

    更新日期:2019-10-01 00:00:00

  • Unpredictable Chronic Mild Stress Paradigm Established Effects of Pro- and Anti-inflammatory Cytokine on Neurodegeneration-Linked Depressive States in Hamsters with Brain Endothelial Damages.

    abstract::The mechanisms by which inflammation affects the different emotional moods are only partially known. Previous works have pointed to stress hormones like glucocorticoids plus the vascular factor endothelin-1 as key factors evoking stressful states especially in relation to endothelial dysfunctions. With this work, it w...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0171-1

    authors: Avolio E,Fazzari G,Mele M,Alò R,Zizza M,Jiao W,Di Vito A,Barni T,Mandalà M,Canonaco M

    更新日期:2017-10-01 00:00:00

  • Comparative Mitochondrial-Based Protective Effects of Resveratrol and Nicotinamide in Huntington's Disease Models.

    abstract::Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacetylase that regulates longevity and enhances mitochondrial metabolism. Both activation and inhibition of SIRT1 were previously shown to ameliorate neuropathological mechanisms in Huntington's disease (HD), a neurodegenerative disease...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0048-3

    authors: Naia L,Rosenstock TR,Oliveira AM,Oliveira-Sousa SI,Caldeira GL,Carmo C,Laço MN,Hayden MR,Oliveira CR,Rego AC

    更新日期:2017-09-01 00:00:00

  • Anti-amyloid Aggregation Activity of Natural Compounds: Implications for Alzheimer's Drug Discovery.

    abstract::Several plant-derived natural compounds are known to exhibit anti-amyloid aggregation activity which makes them attractive as potential therapies to treat Alzheimer's disease. The mechanisms of their anti-amyloid activity are not well known. In this regard, many natural compounds are known to exhibit direct binding to...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-015-9301-4

    authors: Bu XL,Rao PPN,Wang YJ

    更新日期:2016-08-01 00:00:00

  • Synaptic NMDA Receptor Activation Induces Ubiquitination and Degradation of STEP61.

    abstract::NMDA receptor signaling is critical for the development of synaptic plasticity, learning, and memory, and dysregulation of NMDAR signaling is implicated in a number of neurological disorders including schizophrenia (SZ). Previous work has demonstrated that the STriatal-Enriched protein tyrosine Phosphatase 61 kDa (STE...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0555-x

    authors: Xu J,Kurup P,Nairn AC,Lombroso PJ

    更新日期:2018-04-01 00:00:00

  • Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging.

    abstract::Although statins, or hydroxymethylglutaryl coenzyme A (HMG-Co A) reductase inhibitors, are generally used to decrease levels of circulating cholesterol, they have also been reported to have neuroprotective effects through various mechanisms. However, recent results have indicated that they may be harmful in patients w...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-9030-0

    authors: Lee SH,Choi NY,Yu HJ,Park J,Choi H,Lee KY,Huh YM,Lee YJ,Koh SH

    更新日期:2016-01-01 00:00:00

  • Extracellular Vesicles of Alzheimer's Disease Patients as a Biomarker for Disease Progression.

    abstract::Alzheimer's disease (AD) is a progressive neurodegenerative brain pathology and the most common form of dementia. Evidence suggests that extracellular vesicles (EVs) containing cytokines and microRNA are involved in inflammation regulation. The current study aimed to explore a potential impact of AD patients' EVs on d...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02013-1

    authors: Aharon A,Spector P,Ahmad RS,Horrany N,Sabbach A,Brenner B,Aharon-Peretz J

    更新日期:2020-10-01 00:00:00

  • Subcellular localization of mRNA in neuronal cells. Contributions of high-resolution in situ hybridization techniques.

    abstract::The development of technologies for high-resolution nucleic acid localization in cells and tissues has contributed significantly to our understanding of transcriptional and translational regulation in eukaryotic cells. These methods include nonisotopic in situ hybridization methods for light and electron microscopy, a...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/BF02741301

    authors: Martone ME,Pollock JA,Ellisman MH

    更新日期:1998-12-01 00:00:00

  • Calpain-Dependent ErbB4 Cleavage Is Involved in Brain Ischemia-Induced Neuronal Death.

    abstract::Disturbance of neuregulin-1β/ErbB4 signaling is considered to be associated with brain ischemia, but the mechanisms of this disruption are largely unknown. In the present study, we provide evidence that degradation of ErbB4 is involved in neuronal cell death in response to ischemia. Our data showed that the applicatio...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9275-2

    authors: Lu YM,Gao YP,Tao RR,Liao MH,Huang JY,Wu G,Han F,Li XM

    更新日期:2016-05-01 00:00:00

  • The Lesion Analysis of Cholinergic Neurons in 5XFAD Mouse Model in the Three-Dimensional Level of Whole Brain.

    abstract::Cholinergic system is very important for many higher brain functions, including learning and memory. Cholinergic neurons, especially those in the basal forebrain, are specifically susceptible in some neurodegenerative diseases, such as in Alzheimer's disease (AD). Here, we studied the cholinergic system lesion effects...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0621-4

    authors: Yan H,Pang P,Chen W,Zhu H,Henok K A,Li H,Wu Z,Ke X,Wu J,Zhang T,Pan K,Pei L,Han Y,Lu Y

    更新日期:2018-05-01 00:00:00

  • Current progress for the use of miRNAs in glioblastoma treatment.

    abstract::Glioblastoma (GBM) is a highly aggressive brain cancer with the worst prognosis of any central nervous system disease despite intensive multimodal therapy. Inevitably, glioblastoma is fatal, with recurrence of treatment-resistant tumour growth at distal sites leading to an extremely low median survival rate of 12-15 m...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-013-8464-0

    authors: Tivnan A,McDonald KL

    更新日期:2013-12-01 00:00:00

  • Nuclear Factor-kappaB-Dependent Sestrin2 Induction Mediates the Antioxidant Effects of BDNF Against Mitochondrial Inhibition in Rat Cortical Neurons.

    abstract::Brain-derived neurotrophic factor (BDNF), in addition to its neurotrophic action, also possesses antioxidant activities. However, the underlying mechanisms remain to be fully defined. Sestrin2 is a stress-responsive gene implicated in the cellular defense against oxidative stress. Currently, the potential functions of...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9357-1

    authors: Wu CL,Chen SD,Yin JH,Hwang CS,Yang DI

    更新日期:2016-08-01 00:00:00

  • Expression of myostatin in neural cells of the olfactory system.

    abstract::Recent studies show that myostatin mRNA expression is found in some regions of the brain. However, the functional significance of this is currently unknown. We therefore investigated myostatin expression and function in the brain. In this study, we used immunohistochemistry, in situ hybridization, and RT-PCR analysis ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-012-8342-1

    authors: Iwasaki S,Miyake M,Watanabe H,Kitagawa E,Watanabe K,Ohwada S,Kitazawa H,Rose MT,Aso H

    更新日期:2013-02-01 00:00:00

  • Potential Mechanism of Cellular Uptake of the Excitotoxin Quinolinic Acid in Primary Human Neurons.

    abstract::In Alzheimer's disease (AD), excessive amounts of quinolinic acid (QUIN) accumulate within the brain parenchyma and dystrophic neurons. QUIN also regulates glutamate uptake into neurons, which may be due to modulation of Na+-dependent excitatory amino acid transporters (EAATs). To determine the biological relationship...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02046-6

    authors: Braidy N,Alicajic H,Pow D,Smith J,Jugder BE,Brew BJ,Nicolazzo JA,Guillemin GJ

    更新日期:2021-01-01 00:00:00

  • Molecular Association of Glia Maturation Factor with the Autophagic Machinery in Rat Dopaminergic Neurons: a Role for Endoplasmic Reticulum Stress and MAPK Activation.

    abstract::Parkinson's disease (PD) is one of the several neurodegenerative diseases where accumulation of aggregated proteins like α-synuclein occurs. Dysfunction in autophagy leading to this protein build-up and subsequent dopaminergic neurodegeneration may be one of the causes of PD. The mechanisms that impair autophagy remai...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1340-1

    authors: Selvakumar GP,Iyer SS,Kempuraj D,Ahmed ME,Thangavel R,Dubova I,Raikwar SP,Zaheer S,Zaheer A

    更新日期:2019-06-01 00:00:00