Search results for "Alzheimer"

Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse

2020

Alzheimer’s disease (AD) is the most common form of dementia. Besides its cognitive phenotype, AD leads to crucial changes in gut microbiome composition in model mice and in patients, but the reported data are still highly inconsistent. Therefore, we investigated chronic effects of AD-characteristic neurotoxic amyloid-β (Aβ) peptides as provided by transgenic overexpression (5xFAD mouse model) and acute effects due to oral application of Aβ on gut microbes. Astonishingly, one-time feeding of wild type mice with Aβ42 provoked immediate changes in gut microbiome composition (β diversity) as compared to controls. Such obvious changes were not observed when comparing 5xFAD mice with wild type l…

STUDIO DI ASSOCIAZIONE FRA DISLIPIDEMIA, SINDROMI COGNITIVE AMNESTICHE PRE-DEMENZA E MALATTIA DI ALZHEIMER: DATI DI POPOLAZIONE DELLO ZABÙT AGING PRO…

Vascular risk factors in Alzheimer’s disease and Mild Cognitive Impairment: population data from the Zabùt Aging Project

Background: Alzheimer's disease (AD) is the most common cause of dementia in older adults, accounting for about 60% of cases. However, autopsy studies suggested that mixed dementia, with vascular and neurodegenerative AD pathology, accounts for nearly 20% of dementia cases. Aims: Aim of the present study was to evaluate the relationship between isolated or clustered Vascular Risk Factors (VRFs)/diseases and Mild Cognitive Impairment (MCI) or AD. The study was conducted using a Sicilian population-based cohort dataset collected in low-educated, rural subjects, the Zabùt Aging Project (ZAP). The effect-modification by age, sex, education, genetic factor (APOE4 allele carrier), undernutrition,…

Ketogenic diet in neuromuscular and neurodegenerative diseases.

2014

An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson’s disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodege…

Astrocytes Protect Neurons from Aβ1-42 Peptide-Induced Neurotoxicity Increasing TFAM and PGC-1 and Decreasing PPAR-γ and SIRT-1

2015

One of the earliest neuropathological events in Alzheimer's disease is accumulation of astrocytes at sites of Aβ1-42 depositions. Our results indicate that Aβ1-42 toxic peptide increases lipid peroxidation, apoptosis and cell death in neurons but not in astrocytes in primary culture. Aβ1-42-induced deleterious neuronal effects are not present when neurons and astrocytes are mixed cultured. Stimulation of astrocytes with toxic Aβ1-42 peptide increased p-65 and decreased IκB resulting in inflammatory process. In astrocytes Aβ1-42 decreases protein expressions of sirtuin 1 (SIRT-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) and over-expresses peroxisome proliferator-activated re…

Detecting global and local hippocampal shape changes in Alzheimer's disease using statistical shape models.

2012

Item does not contain fulltext The hippocampus is affected at an early stage in the development of Alzheimer's disease (AD). With the use of structural magnetic resonance (MR) imaging, we can investigate the effect of AD on the morphology of the hippocampus. The hippocampal shape variations among a population can be usually described using statistical shape models (SSMs). Conventional SSMs model the modes of variations among the population via principal component analysis (PCA). Although these modes are representative of variations within the training data, they are not necessarily discriminative on labeled data or relevant to the differences between the subpopulations. We use the shape des…

Alzheimer: A Decade of Drug Design. Why Molecular Topology can be an Extra Edge?

2017

Background The last decade was characterized by a growing awareness about the severity of dementia in the field of age-related and no age-related diseases and about the importance to invest resources in the research of new, effective treatments. Among the dementias, Alzheimer's plays a substantial role because of its extremely high incidence and fatality. Several pharmacological strategies have been tried but still now, Alzheimer keeps being an untreatable disease. In literature, the number of QSAR related drug design attempts about new treatments for Alzheimer is huge, but only few results can be considered noteworthy. Providing a detailed analysis of the actual situation and reporting the…

Molecular topology as novel strategy for discovery of drugs with aβ lowering and anti-aggregation dual activities for Alzheimer's disease.

2014

Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy. Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multifunctional single agent compounds, in this case, the dual func…

DesMol2, an Effective Tool for the Construction of Molecular Libraries and Its Application to QSAR Using Molecular Topology

2019

A web application, DesMol2, which offers two main functionalities, is presented: the construction of molecular libraries and the calculation of topological indices. These functionalities are explained through a practical example of research of active molecules to the formylpeptide receptor (FPR), a receptor associated with chronic inflammation in systemic amyloidosis and Alzheimer&rsquo

Nanoparticulate Systems for Drug Delivery and Targeting to the Central Nervous System

2010

Brain delivery is one of the major challenges for the neuropharmaceutical industry since an alarming increase in brain disease incidence is going on. Despite major advances in neuroscience, many potential therapeutic agents are denied access to the central nervous system (CNS) because of the existence of a physiological low permeable barrier, the blood-brain barrier (BBB). To obtain an improvement of drug CNS performance, sophisticated approaches such as nanoparticulate systems are rapidly developing. Many recent data demonstrate that drugs could be transported successfully into the brain using colloidal systems after i.v. injection by several mechanisms such as endocytosis or P-glycoprotei…