Search results for " Alzheimer's disease"
showing 10 items of 41 documents
LRP1 mediates bidirectional transcytosis of amyloid-β across the blood-brain barrier.
2011
According to the "amyloid hypothesis", the amyloid-β (Aβ) peptide is the toxic intermediate driving Alzheimer's disease (AD) pathogenesis. Recent evidence suggests that the low density lipoprotein receptor-related protein 1 (LRP1) transcytoses Aβ out of the brain across the blood-brain barrier (BBB). To provide genetic evidence for LRP1-mediated transcytosis of Aβ across the BBB we analyzed Aβ transcytosis across primary mouse brain capillary endothelial cells (pMBCECs) derived from wild-type and LRP1 knock-in mice. Here, we show that pMBCECs in vitro express functionally active LRP1. Moreover, we demonstrate that LRP1 mediates transcytosis of [(125)I]-Aβ(1-40) across pMBCECs in both direct…
EFFETTO DEGLI ESTRATTI DI PAPAYA FERMENTATA SULLO STRESS OSSIDATIVO IN PAZIENTI CON MALATTIA DI ALZHEIMER
2013
Brain tissue is particularly susceptible to oxidative damage, which has been associated with pathological findings of Alzheimer's disease (AD), such as amyloid plaques and protein fibrils. Oxidative stress alterations, including increased production of reactive oxygen metabolites, decline of antioxidant systems, and decreased efficiency in repairing molecules, have been linked to the development of AD. Postmortem studies on brain tissue from AD patients have shown several oxidative damage markers, such as increased lipid peroxidation, oxidative damage of proteins, glyco-oxidation, and reduction of antioxidant systems. We studied 40 patients referred to our Geriatric Unit (age 78,2 ± 1,1 yea…
Metabolite profile and in vitro activities of Phagnalon saxatile (L.) Cass. relevant to treatment of Alzheimer’s disease
2009
The present study describes for the first time the in vitro properties (inhibition of NO production and anticholinesterase) of Phagnalon saxatile (L.) Cass. (Asteraceae). The methanolic extract showed antioxidant activity that was measured by DPPH assay and beta-carotene bleaching test. The same extract inhibited NO production in the murine monocytic macrophage cell line RAW 264.7. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition was assessed by modifications of Ellman's method. Purification of the MeOH extract of P. saxatile allowed the isolation of phenolic compounds. Among them, the compounds that most effectively inhibited lipopolysaccharide-induced NO production …
Lipofuscin Hypothesis of Alzheimer’s Disease
2011
The primary culprit responsible for Alzheimer’s disease (AD) remains unknown. Aβ protein has been identified as the main component of amyloid of senile plaques, the hallmark lesion of AD, but it is not definitively established whether the formation of extracellular Aβ deposits is the absolute harbinger of the series of pathological events that hit the brain in the course of sporadic AD. The aim of this paper is to draw attention to a relatively overlooked age-related product, lipofuscin, and advance the hypothesis that its release into the extracellular space following the death of neurons may substantially contribute to the formation of senile plaques. The presence of intraneuronal Aβ, sim…
Inflammation, genes and zinc in Alzheimer's disease.
2007
Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia. AD has been linked to inflammation and metal biological pathway. Neuro-pathological hallmarks are senile plaques, resulting from the accumulation of several proteins and an inflammatory reaction around deposits of amyloid, a fibrillar protein, Abeta, product of cleavage of a much larger protein, the beta-amyloid precursor protein (APP) and neurofibrillary tangles. Amyloid deposition, due to the accumulation of Abeta peptide, is the main pathogenetic mechanism. Inflammation clearly occurs in pathologically vulnerable regions of AD and several i…
The Contribution of Microscopy to the Study of Alzheimer’s Disease, Amyloid Plaques and Aβ Fibrillogenesis
2006
A broad survey is presented in this chapter, dealing with the impact that microscopy has made to the study of Alzheimer’s disease, amyloid plaques and amyloid-β fibrillogenesis. This includes classical light microscopy and the modern immunolabelling and confocal microscopies, together with the contribution of transmission electron microscopy and atomic force microscopy. Whilst usefully standing alone, the individual microscopies often contribute most effectively when they are integrated with cellular, biophysical and molecular approaches.
Expression of the Anti-amyloidogenic Secretase ADAM10 Is Suppressed by Its 5′-Untranslated Region*
2010
Proteolytic processing of the amyloid precursor protein by alpha-secretase prevents formation of the amyloid beta-peptide (Abeta), which is the main constituent of amyloid plaques in brains of Alzheimer disease (AD) patients. alpha-Secretase activity is decreased in AD, and overexpression of the alpha-secretase ADAM10 (a disintegrin and metalloprotease 10) in an AD animal model prevents amyloid pathology. ADAM10 has a 444-nucleotide-long, very GC-rich 5'-untranslated region (5'-UTR) with two upstream open reading frames. Because similar properties of 5'-UTRs are found in transcripts of many genes, which are regulated by translational control mechanisms, we asked whether ADAM10 expression is…
Reduced graphene oxide decorated with metals nanoparticles electrode as electrochemical sensor for dopamine
2019
Dopamine (DA) is one of the most important neurotransmitters that influences the processes that involve memory, sleep, mood, learning among others [1]. In fact, in the last years, dopamine concentration in human body fluids has been related to some neurodegenerative diseases, such as Parkinson and Alzheimer's diseases [2]. The possibility to have a bio-marker for these disease is of extreme importance because, disease related with dementia, are diagnosed when they are already developed and their management become almost impossible. The possibility to continuously monitor DA level in fluids, such as blood and urine, could accelerate the early diagnosis of these diseases. The principal analyt…
Synthesis and characterization of a new insulin conjugated nanogel for biomedical application
2015
Insulin, a metabolic hormone involved in glucose metabolism, plays also a neuroprotective role in the central nervous system being able to revert the cytotoxic processes induced by Aβ42,a peptide involved in Alzheimer's disease. To reach the brain insulin have to across the BBB therefore an additional delivery strategy results to be necessary. For these aim we performed an insulin conjugated nanogels (NGs-In). Nanogels (NGs) have a great potential in the development of “smart” nanocarriers for (bio)molecular drugs and contrast agent for bioimaging. They are formed by physically or chemically crosslinked polymer networks, characterized by a large and flexible surface available for multivalen…
18F-Florbetaben PET/CT to Assess Alzheimer's Disease: A new Analysis Method for Regional Amyloid Quantification.
2019
Background and purpose While AD can be definitively confirmed by postmortem histopathologic examination, in vivo imaging may improve the clinician's ability to identify AD at the earliest stage. The aim of the study was to test the performance of amyloid PET using new processing imaging algorithm for more precise diagnosis of AD. Methods Amyloid PET results using a new processing imaging algorithm (MRI-Less and AAL Atlas) were correlated with clinical, cognitive status, CSF analysis, and other imaging. The regional SUVR using the white matter of cerebellum as reference region and scores from clinical and cognitive tests were used to create ROC curves. Leave-one-out cross-validation was carr…