Search results for " ALZHEIMER"

Insulin Nanogel as New Strategy for the Treatment of Alzheimer’s Disease

2015

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in neuronal degeneration associated with Alzheimer's disease (AD). Thus, the administration of insulin to the brain could be a strategy for the prevention and treatment of AD disease. With this aim, we have designed, synthesized and characterized a nanogel system (NG) that can be used as substrate for the conjugation of insulin and/or fluorescent molecules relevant for their characterization. In particular, a carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system, has been produced by ionizing radiation starting from th…

Designing trehalose-conjugated peptides for the inhibition of Alzheimer’s Aβ oligomerization and neurotoxicity

2008

Implications of alpha- and beta-secretase expression and function in Alzheimer's disease

2020

Abstract There has been intense debate in the field about the extent to which processing of the amyloid precursor protein contributes to pathogenesis of Alzheimer's disease. Early publications succeeding in the identification of the main component of senile plaques—the amyloid-beta (A-beta) peptide—strictly argued for a constitutive contribution of A-beta to disease initiation and progression. This led to development of the amyloid hypothesis, which in recent years was attacked for the lack of success of clinical studies based on the respective assumption. There is evidence that the hypothesis must be revisited, but accumulation of A-beta along with aging might still be the best explanation…

Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer׳s disease

2015

Neurofibrillary tangles (aggregates of cytoskeletal Tau protein) and senile plaques (aggregates mainly formed by amyloid β peptide) are two landmark lesions in Alzheimer׳s disease. Some researchers have proposed tangles, whereas others have proposed plaques, as primary lesions. For a long time, these were thought of as independent mechanisms. However, experimental evidence suggests that both lesions are intimately related. We review here some molecular pathways linking amyloid β and Tau toxicities involving, among others, glycogen synthase kinase 3β, p38, Pin1, cyclin-dependent kinase 5, and regulator of calcineurin 1. Understanding amyloid β and Tau toxicities as part of a common pathophys…

Depressive Symptom Profiles Predict Specific Neurodegenerative Disease Syndromes in Early Stages

2020

Background: During early stages, patients with neurodegenerative diseases (NDG) often present with depressive symptoms. However, because depression is a heterogeneous disorder, more precise delineation of the specific depressive symptom profiles that arise early in distinct NDG syndromes is necessary to enhance patient diagnosis and care. Methods and Findings: Five-hundred and sixty four participants self-reported their depressive symptoms using the Geriatric Depression Scale (GDS), including 111 healthy older control subjects (NC) and 453 patients diagnosed with one of six NDGs who were at the mild stage of disease (CDR® Dementia Staging Instrument ≤ 1) [186 Alzheimer's disease (AD), 76 be…

ORAL HEALTH STATUS AND PERIODONTITIS IN ALZHEIMER'S DISEASE:A POPULATION-BASED, CASE-CONTROL STUDY FROM THE ZABUT AGING PROJECT

2014

Aims. The aetiopathogenesis for Alzheimer's disease (AD) have not been defined, although inflammation within the brain is thought to play a role. Recent data suggest that peripheral infections contribute to the inflammatory state of central nervous system diseases, including cognitive impairment and dementia (1). Periodontitis (PD) is a prevalent, chronic infection involving the tissues supporting the teeth associated with gram negative, anaerobic bacteria capable of promoting local and systemic release of inflammatory mediators. Aim of the present study was to assess the oral health status and the prevalence/severity of PD in incident AD subjects evaluated during a population-based, 10-yea…

Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders

2011

In recent years, there has been a growing interest, supported by a large number of experimental and epidemi-ological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces…

Thioflavin T templates amyloid β(1–40) conformation and aggregation pathway

2015

Aβ(1-40) peptide supramolecular assembly and fibril formation processes are widely recognized to have direct implications in the progression of Alzheimer's disease. The molecular basis of this biological process is still unknown and there is a strong need of developing effective strategies to control the occurring events. To this purpose the exploitation of small molecules interacting with Aβ aggregation represents one of the possible routes. Moreover, the use specific labeling has represented so far one of the most common and effective methods to investigate such a process. This possibility in turn rests on the reliability of the probe/labels involved. Here we present evidences of the effe…

Evaluation of Alpha-Synuclein Cerebrospinal Fluid Levels in Several Neurological Disorders

2022

(1) Background: Alpha-synuclein (α-syn) is a presynaptic neuronal protein that regulates several neuronal functions. In recent decades, the role of α-syn as a biomarker of neurodegenerative diseases has been explored, especially in synucleinopathies. However, only a few studies have assessed its role as biomarker in other neurological disorders. The aim of the study was to evaluate cerebrospinal fluid (CSF) α-syn levels in several neurological disorders; (2) Methods: We measured CSF α-syn levels by a commercial ELISA kit in 158 patients classified in the following group: controls, Alzheimer’s Disease (AD), cerebrovascular diseases, inflammatory central nervous …

Composti curcumin-like come agenti neuro-protettori. Interazione con HSP60

2014

La Malattia di Alzheimer rappresenta una sfida fondamentale del XXI secolo per la salute pubblica. Le terapie attualmente utilizzate per la cura dell’Alzheimer si basano sugli aspetti sintomatici della patologia [1]. Un importante ruolo nella malattia è rivestito dalle Heat shock proteins (HSPs), proteine che presiedono al controllo del ripiegamento proteico [2]. Recentemente, è stato dimostrato che HSP60 media la traslocazione del Precursore della Proteina Amiloide (APP) e del Peptide Beta Amiloide (Aβ) nei mitocondri, portando alla perdita della funzionalità dell’organulo [3]. Nel campo degli approcci delle terapie potenziali, la curcumina sta emergendo come lead compound per lo sviluppo …