Search results for "Alzheimer’s"
showing 10 items of 122 documents
Involvement of Kv3.1 potassium chanels in 7-ketocholesterol, 24S-hydroxycholesterol and C24 : 0-induced lipotoxicity on 158N and BV-2 cells : relatio…
2017
Potassium (K+) is involved in the regulation of cellular excitability, cell cycle regulation, cell viability, neuroprotection and maintenance of microglial and oligodendrocytic functions. Potassium dysfunction, described in several neurodegenerative diseases such as Alzheimer's Disease (AD), multiple sclerosis (MS), Parkinson's disease and Huntington's disease, may be a potential therapeutic target. The underlying toxic mechanisms of these neurodegenerative pathologies involve oxysterols, which are oxidized cholesterol derivatives, and fatty acids including those associated with peroxisomal metabolism. 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC) and tetracosanoic acid (C24:0),…
Aß(25-35) and its C-and/or N-blocked derivatives: copper driven structural features and neurotoxicity
2006
The toxic properties of beta-amyloid protein, Abeta(1-42), the major component of senile plaques in Alzheimer's disease, depend on nucleation-dependent oligomerization and aggregation. In addition, Abeta(1-42) toxicity is favored by the presence of trace metals, which affect the secondary structure of the peptide. A peptide comprising 11 residues within Abeta(1-42) [Abeta(25-35)] aggregates and retains the neurotoxic activity of Abeta(1-42). We have used both Abeta(25-35) and its C-amidated or N-acetylated/C-amidated derivatives to investigate the role of copper(II) in modulating the conformation and aggregation state as well as the neurotoxic properties of amyloid peptides. Electrospray io…
What's Curcumin's mind? The potential role of Curcuminoids in the treatment of Alzheimer's disease
2020
Neurodegenerative diseases (NDs) are one of major public health problems and their impact is continuously growing. Curcumin has been proposed for the treatment of several of these pathologies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) due to the ability of this molecule to reduce inflammation and aggregation of involved proteins. Nevertheless, the poor metabolic stability and bioavailability of curcumin reduce the possibilities of its practical use. In this review will be highlighted recent results on curcumin and curcuminoids in the search of new effective therapeutic agents against NDs, with particular emphasis on AD.
The Effectiveness of Vitamin E Treatment in Alzheimer’s Disease
2019
Vitamin E was proposed as treatment for Alzheimer’s disease many years ago. However, the effectiveness of the drug is not clear. Vitamin E is an antioxidant and neuroprotector and it has anti-inflammatory and hypocholesterolemic properties, driving to its importance for brain health. Moreover, the levels of vitamin E in Alzheimer’s disease patients are lower than in non-demented controls. Thus, vitamin E could be a good candidate to have beneficial effects against Alzheimer’s. However, evidence is consistent with a limited effectiveness of vitamin E in slowing progression of dementia; the information is mixed and inconclusive. The question is why does vitamin E fail to tre…
Galantamine delivery on buccal mucosa: permeation enhancement and design of matrix tablets
2009
The most important feature in transbuccal drug delivery is the low drug passage through the buccal mucosa. In our previous work we demonstrated the aptitude of Galantamine to penetrate the buccal tissue. The collected data suggested that Galantamine passively crosses the membrane, but the calculated Js and Kp values showed that the drug amount that crosses the membrane wasn’t sufficient to assure blood therapeutic level. So, in this study, ex vivo permeation tests, using porcine buccal mucosa, were performed in presence of physical or chemical enhancers. No significant differences in penetration rate were observed using chemical enhancers as sodium dehydrocholate, EDTA disodium salt and tri…
Losing DNA methylation at repetitive elements and breaking bad
2021
Abstract Background DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability (including chromosome stability) by controlling both gene expression and chromatin structure. Therefore, the onset of an incorrect pattern of DNA methylation is potentially dangerous for the cells. This is particularly important with respect to repetitive elements, which constitute the third of the human genome. Main body Repetitive sequences are involved in several cell processes, however, due to their intrinsic nature, they can be a source of genome instability. Thus, most repetitive elements are usually meth…
GSK3β overexpression induces neuronal death and a depletion of the neurogenic niches in the dentate gyrus
2010
Overexpression of GSK3β in transgenic mice induces learning deficits and some features associated with Alzheimer's disease (AD), including dentate gyrus (DG) atrophy. Here, we assessed whether these mice also recapitulate DG atrophy as well as impaired neurogenesis reported in AD. Ultrastructural analysis revealed that there were fewer and more disorganized neurogenic niches in these animals, coupled with an increase in the proportion of immature neurons. Indeed, the maturation of granule cells is delayed as witnessed by the alterations to the length and patterning of their dendritic trees and to the mossy fiber terminals. Together with an increase in neuronal death, these phenomena lead to…
Role of prothrombotic polymorphisms in successful or unsuccessful aging.
2011
The study of the genetic profile of centenarians aims to identify the genes and allelic variants which may influence a greater life expectancy and that can be considered as predisposing factors associated to the aging diseases, such as Alzheimer. Centenarians, that represent a cohort of selected survivors, show an hypercoagulability state characterised by striking signs of high coagulation enzyme activity, as directly assessed by the tested higher plasma level of some important factors involved in the haemostasis balance. Anyway, these individuals seem to have a reduced susceptibility to dementia, as well as to cardiovascular events. In this study we analyze the frequencies of Leiden Factor…
Predictors of Falls and Fractures Leading to Hospitalization in People With Dementia: A Representative Cohort Study.
2018
OBJECTIVES: Investigate predictors of falls and fractures leading to hospitalization in a large cohort of people with dementia. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: People with diagnosed dementia between January 2007 and March 2013, aged >65 years, were assembled using data from the Maudsley Biomedical Research Centre Case Register, from 4 boroughs in London serving a population of 1.3 million people. MEASURES: Falls and/or fractures leading to hospitalization were ascertained from linked national records. Demographic data, cognitive test scores, medications, and symptom and functioning scores from Health of the Nation Outcome Scales (HoNOS65+) were modeled in mul…
Immunosenescence, inflammation and Alzheimer’s disease
2012
Abstract Ageing impacts negatively on the development of the immune system and its ability to fight pathogens. Progressive changes in the T-cell and B-cell systems over the lifespan of individuals have a major impact on the capacity to respond to immune challenges. The cumulative age-associated changes in immune competence are termed immunosenescence that is characterized by changes where adaptive immunity deteriorates, while innate immunity is largely conserved or even upregulated with age. On the other hand, ageing is also characterized by “inflamm-ageing”, a term coined to explain the inflammation commonly present in many age-associated diseases. It is believed that immune inflammatory p…