nNOS Expression in Reactive Astrocytes Correlates with Increased Cell Death Related DNA Damage in the Hippocampus and Entorhinal Cortex in Alzheimer's Disease

2000 ◽  
Vol 165 (1) ◽  
pp. 12-26 ◽  
Author(s):  
Goran Šimić ◽  
Paul J. Lucassen ◽  
Željka Krsnik ◽  
Božo Krušlin ◽  
Ivica Kostović ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Damage ◽  
Cell Death ◽  
Entorhinal Cortex ◽  
Reactive Astrocytes ◽  
Nnos Expression

scholarly journals HMGB1 signaling phosphorylates Ku70 and impairs DNA damage repair in Alzheimer’s disease pathology

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hikari Tanaka ◽  
Kanoh Kondo ◽  
Kyota Fujita ◽  
Hidenori Homma ◽  
Kazuhiko Tagawa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Damage ◽  
Cell Death ◽  
Transcriptional Repression ◽  
Dna Damage Repair ◽  
High Mobility ◽  
Hmgb1 Protein ◽  
Atypical Cell ◽  
Damage Repair

AbstractDNA damage is increased in Alzheimer’s disease (AD), while the underlying mechanisms are unknown. Here, we employ comprehensive phosphoproteome analysis, and identify abnormal phosphorylation of 70 kDa subunit of Ku antigen (Ku70) at Ser77/78, which prevents Ku70-DNA interaction, in human AD postmortem brains. The abnormal phosphorylation inhibits accumulation of Ku70 to the foci of DNA double strand break (DSB), impairs DNA damage repair and eventually causes transcriptional repression-induced atypical cell death (TRIAD). Cells under TRIAD necrosis reveal senescence phenotypes. Extracellular high mobility group box 1 (HMGB1) protein, which is released from necrotic or hyper-activated neurons in AD, binds to toll-like receptor 4 (TLR4) of neighboring neurons, and activates protein kinase C alpha (PKCα) that executes Ku70 phosphorylation at Ser77/78. Administration of human monoclonal anti-HMGB1 antibody to post-symptomatic AD model mice decreases neuronal DSBs, suppresses secondary TRIAD necrosis of neurons, prevents escalation of neurodegeneration, and ameliorates cognitive symptoms. TRIAD shares multiple features with senescence. These results discover the HMGB1-Ku70 axis that accounts for the increase of neuronal DNA damage and secondary enhancement of TRIAD, the cell death phenotype of senescence, in AD.

Is it All Said for NSAIDs in Alzheimer’s Disease? Role of Mitochondrial Calcium Uptake

2018 ◽  
Vol 15 (6) ◽  
pp. 504-510 ◽  
Author(s):  
Sara Sanz-Blasco ◽  
Maria Calvo-Rodríguez ◽  
Erica Caballero ◽  
Monica Garcia-Durillo ◽  
Lucia Nunez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Amyloid Β ◽  
Epidemiological Data ◽  
Amyloid Β Peptide ◽  
Aβ Oligomers ◽  
Mitochondrial Potential ◽  
Disease Modifying Drugs ◽  
Definitive Evidence

Objectives: Epidemiological data suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD). Unfortunately, recent trials have failed in providing compelling evidence of neuroprotection. Discussion as to why NSAIDs effectivity is uncertain is ongoing. Possible explanations include the view that NSAIDs and other possible disease-modifying drugs should be provided before the patients develop symptoms of AD or cognitive decline. In addition, NSAID targets for neuroprotection are unclear. Both COX-dependent and independent mechanisms have been proposed, including γ-secretase that cleaves the amyloid precursor protein (APP) and yields amyloid β peptide (Aβ). Methods: We have proposed a neuroprotection mechanism for NSAIDs based on inhibition of mitochondrial Ca2+ overload. Aβ oligomers promote Ca2+ influx and mitochondrial Ca2+ overload leading to neuron cell death. Several non-specific NSAIDs including ibuprofen, sulindac, indomethacin and Rflurbiprofen depolarize mitochondria in the low µM range and prevent mitochondrial Ca2+ overload induced by Aβ oligomers and/or N-methyl-D-aspartate (NMDA). However, at larger concentrations, NSAIDs may collapse mitochondrial potential (ΔΨ) leading to cell death. Results: Accordingly, this mechanism may explain neuroprotection at low concentrations and damage at larger doses, thus providing clues on the failure of promising trials. Perhaps lower NSAID concentrations and/or alternative compounds with larger dynamic ranges should be considered for future trials to provide definitive evidence of neuroprotection against AD.

Strawberry ( Fragaria ananassa duch.) Alba extract attenuates DNA damage in lymphocytes of patients with Alzheimer’s disease

2021 ◽  
Author(s):  
Lada Živković ◽  
Vladan Bajić ◽  
Andrea Čabarkapa‐Pirković ◽  
Dragana Dekanski ◽  
Tamara Yuliett Forbes‐Hernández ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Damage ◽  
Fragaria Ananassa

scholarly journals Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model

2020 ◽  
Vol 13 (10) ◽  
pp. 288
Author(s):  
Marielza Andrade Nunes ◽  
Mariana Toricelli ◽  
Natalia Mendes Schöwe ◽  
Helena Nascimento Malerba ◽  
Karis Ester Dong-Creste ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Functional Disability ◽  
Therapeutic Option ◽  
Receptor Activation ◽  
Hippocampal Culture ◽  
Kinin System ◽  
Organotypic Hippocampal Culture ◽  
Kallikrein Kinin System

Background: Alzheimer’s disease is mainly characterized by remarkable neurodegeneration in brain areas related to memory formation. This progressive neurodegeneration causes cognitive impairment, changes in behavior, functional disability, and even death. Our group has demonstrated changes in the kallikrein–kinin system (KKS) in Alzheimer’s disease (AD) experimental models, but there is a lack of evidence about the role of the KKS in Alzheimer’s disease. Aim: In order to answer this question, we evaluated the potential of the kinin B2 receptors (BKB2R) to modify AD characteristics, particularly memory impairment, neurodegeneration, and Aβ peptide deposition. Methods: To assess the effects of B2, we used transgenic Alzheimer’s disease mice treated with B2 receptor (B2R) agonists and antagonists, and performed behavioral and biochemical tests. In addition, we performed organotypic hippocampal culture of wild-type (WT) and transgenic (TG) animals, where the density of cytokines, neurotrophin BDNF, activated astrocyte marker S100B, and cell death were analyzed after treatments. Results: Treatment with the B2R agonist preserved the spatial memory of transgenic mice and decreased amyloid plaque deposition. In organotypic hippocampal culture, treatment with B2R agonist decreased cell death, neuroinflammation, and S100B levels, and increased BDNF release. Conclusions: Our results indicate that the kallikrein–kinin system plays a beneficial role in Alzheimer’s disease through B2R activation. The use of B2R agonists could, therefore, be a possible therapeutic option for patients diagnosed with Alzheimer’s disease.

P1-178: Early astrocytic atrophy in the Entorhinal cortex of a triple transgenic animal model of Alzheimer's disease

2010 ◽  
Vol 6 ◽  
pp. S225-S225
Author(s):  
Chia-Yu Yeh ◽  
Markel Olabarria ◽  
Harun N. Noristani ◽  
Alexei Verkhratsky ◽  
Jose J. Rodriguez
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Entorhinal Cortex ◽  
Transgenic Animal ◽  
Transgenic Animal Model ◽  
Model Of Alzheimer’S Disease

Predicting Alzheimer's Disease Progression by Combining Multiple Measures

2021 ◽  
Author(s):  
Nour Zawawi ◽  
Heba Gamal Saber ◽  
Mohamed Hashem ◽  
Tarek F.Gharib
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Early Diagnosis ◽  
Nerve Cell ◽  
Neurological Examination ◽  
Medical Data ◽  
Complex Interactions ◽  
Dementia Patients ◽  
Nerve Cell Death

Alzheimer's disease (AD) is a degenerative brain ailment that affects millions worldwide. It is the most common form of dementia. Patients with an early diagnosis of Alzheimer's disease have a strong chance of preventing additional brain damage by halting nerve cell death. At the same time, it begins to progress several years before any symptoms appear. The variety of data is the biggest problem encountered during diagnosis. Neurological examination, brain imaging, and often asked questions from his connected closed relatives are the three forms of data that a neurologist or geriatrics employs to diagnose patients. One of the biggest questions which need answering is the choice of a convenient feature. The main objective of this paper is to help neurologists or geriatricians diagnose patient conditions. It proposes a new hybrid model for features extracted from medical data. It discusses AD's early diagnosis and progression for all features considered in the diagnosis and their complex interactions. It proves to have the best accuracy when compared with the state-ofthe-art algorithm. Also, it proves to be more accurate against some recent research ideas. It got 95% in all cases, considering this work focused more on increasing the number of instances in comparison.

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