Search results for "YLOID"

Antioxidants as a Potential Therapy Against Age-Related Neurodegenerative Diseases: Amyloid Beta Toxicity and Alzheimers Disease

2006

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disorder with distinct neuropathological features. Extracellular plaques, consisting of aggregated amyloid peptides of 39-43 amino acids are one of the most prominent pathological hallmarks of this disease. Although the exact neurochemical effector mechanism of Abeta aggregation is not yet elucidated, age-associated disturbances of metal ion metabolism have been proposed to promote the formation of aggregates from soluble Abeta. Oxidative stress is postulated to be a downstream effect of Abeta-metal ion interactions. Therefore, the modulation of brain metal metabolism and attenuation of oxidative stress by antioxidant m…

Cannabinoid receptor 1 deficiency in a mouse model of Alzheimer's disease leads to enhanced cognitive impairment despite of a reduction in amyloid de…

2012

Alzheimer's disease (AD) is characterized by amyloid-beta deposition in amyloid plaques, neurofibrillary tangles, inflammation, neuronal loss, and cognitive deficits. Cannabinoids display neuromodulatory and neuroprotective effects and affect memory acquisition. Here, we studied the impact of cannabinoid receptor type 1 (CB1) deficiency on the development of AD pathology by breeding amyloid precursor protein (APP) Swedish mutant mice (APP23), an AD animal model, with CB1-deficient mice. In addition to the lower body weight of APP23/CB1(-/-) mice, most of these mice died at an age before typical AD-associated changes become apparent. The surviving mice showed a reduced amount of APP and its …

ADAM-10 over-expression increases cortical synaptogenesis.

2006

Cortical cholinergic, glutamatergic and GABAergic terminals become upregulated during early stages of the transgenic amyloid pathology. Abundant evidence suggests that sAPP alpha, the product of the non-amyloidogenic alpha-secretase pathway, is neurotrophic both in vitro and when exogenously applied in vivo. The disintegrin metalloprotease ADAM-10 has been shown to have alpha-secretase activity in vivo. To determine whether sAPP alpha has an endogenous biological influence on cortical presynaptic boutons in vivo, we quantified cortical cholinergic, glutamatergic and GABAergic presynaptic bouton densities in either ADAM-10 moderate expressing (ADAM-10 mo) transgenic mice, which moderately ov…

Design, Synthesis, and Biological Evaluation of Novel Fluorinated Ethanolamines

2011

The preparation of novel fluorinated allylamines and their use as key fragments for the stereoselective synthesis of hydroxyethyl secondary amine (HEA)-type peptidomimetics is described. Our strategy employs chiral sulfinyl imines as synthesis intermediates, by treatment of hemiaminal precursors with two equivalents of vinylmagnesium bromide. The subsequent oxidation of the allylic amines to the corresponding epoxides was achieved by treatment with methyl(trifluoromethyl)dioxirane. Finally, epoxide ring opening with a range of nitrogen nucleophiles provided a library of HEA-derived peptidomimetics with a phenyldifluoromethylene moiety. The biological evaluation of these derivatives revealed…

CHARACTERIZATION OF THE SYNAPTIC PROTEOME IN NON-DEMENTED SUBJECTS WITH ALZHEIMER’S NEUROPATHOLOGY

Some individuals, here refereed to as Non-Demented with Alzheimer’s Neuropathology (NDAN), retain their congitive function despite the presence of amyloid plaques and tau tangles typical of symptomatic Alzheimer’s Disease (AD). In NDAN, unlike AD, toxic amyloid beta oligomers do not localize to the postsynaptic densities (PSDs). Synaptic resistance to amyloid beta in NDAN may thus enable these individuals to remain cognitively intact despite the AD-like pathology. The mechanim(s) responsible for this resistance remains unresolved and understanding such protective biological processes could reveal novel targets for the development of effective treatments for AD. The current work describes th…

SYNTHESIS AND EVALUATION OF CURCUMIN ANALOGUES AS NEURO-PROTECTIVE AGENTS FOR THE ALZHEIMER'S DISEASE

2013

The Alzheimer's disease (AD) is the most common form of senile dementia.1 The most important role in AD is played by the aggregation process of beta-amyloid peptide (Aß), responsible for the cytotoxic effects.2 In this context, the purpose of this study was to synthesize new dicarbonyl compounds 1 structurally related to curcumin3, with anti-aggregation activity against Aß.Parallel studies involve the synthesis of heterocyclic-based curcumin-like molecules that are currently under investigation by means of in silico protocols in order to rationalize the ligand-biological target interactions.

Targeting Alzheimer’s disease with multimodal polypeptide-based nanoconjugates

2021

LRP1-targeted St-Cl–polyglutamate conjugates as multivalent neuroprotective/neurotrophic therapeutics for Alzheimer’s disease.

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders

2022

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn…

Amyloid Fibrils Formation of Concanavalin A at Basic pH

2011

Mechanisms of partial unfolding and aggregation of proteins are of extreme interest in view of the fact that several human pathologies are characterized by the formation and deposition of protein-insoluble material, mainly composed of amyloid fibrils. Here we report on an experimental study on the heat-induced aggregation mechanisms, at basic pH, of concanavalin A (ConA), used as a model system. Thioflavin T (ThT) fluorescence and multiangle light scattering allowed us to detect different intertwined steps in the formation of ConA aggregates. In particular, the ThT fluorescence increase, observed in the first phase of aggregation, reveals the formation of intermolecular β-sheet structure wh…

Therapy of ATTR Cardiac Amyloidosis: Current Indications

2023

Transthyretin cardiac amyloidosis is a restrictive cardiomyopathy caused by extracellular deposition in the heart of amyloid fibrils derived from plasma transthyretin (ATTR), either in its hereditary (ATTRh) or acquired (ATTRwt) forms. Cardiac amyloidosis has a very poor prognosis if therapy is not started promptly. Therefore, it is very important to recognize cardiac amyloidosis early in order to immediately start a treatment capable of modifying the prognosis. Treatment of cardiac amyloidosis is not easy, often requiring a multidisciplinary team. New RNA-interfering drugs (such as patisiran) have been devised and are effective in the treatment of ATTRh amyloidosis. Tafamidis (a stabilizer…