Search results for "Tau protein"
showing 10 items of 48 documents
Modulating disease-relevant tau oligomeric strains by small molecules
2020
The pathological aggregation of tau plays an important role in Alzheimer's disease and many other related neurodegenerative diseases, collectively referred to as tauopathies. Recent evidence has demonstrated that tau oligomers, small and soluble prefibrillar aggregates, are highly toxic due to their strong ability to seed tau misfolding and propagate the pathology seen across different neurodegenerative diseases. We previously showed that novel curcumin derivatives affect preformed tau oligomer aggregation pathways by promoting the formation of more aggregated and nontoxic tau aggregates. To further investigate their therapeutic potential, we have extended our studies o disease-relevant bra…
Brain aging and late-onset Alzheimer's disease: many open questions.
2012
ABSTRACTDespite decades of research in the field of Alzheimer's disease (AD), a real understanding of its molecular pathophysiology and treatments relevant to the day-to-day lives of patients remain out of reach. Research has, with good reason, focused on certain key pathways and potential mechanisms, but sometimes this has been at the expense of work on other theories, which may be slowing down progress in this field. Interesting theories at present include oxidative stress and caloric restriction. Work on the Aβ cascade should continue but with a shift in focus to its intracellular effects and an awareness that additional pathogenetic factors and processes must be involved – most importan…
Alzheimer’s disease and infections, where we stand and where we go
2014
Editorial Alzheimer’s disease (AD) is a progressive neurological disorder, which represents the most common form of dementia, one of the major causes of disability in later life. Age is the greatest risk factor for AD, which typically affects people aged 65 years and over, with an age-standardised prevalence of 4.4 [1]. However, AD is not a normal part of ageing and advanced age alone does not justify the disease. Several pathways have been implicated in AD pathophysiology, the most described is the neurodegenerative one, which lead to the brain accumulation of beta-amyloid and neurofibrillary tangles, aggregations of hyperphosphorylated tau protein, macroscopically resulting in brain atrop…
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-β toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer's disease.
2011
Amyloid-β peptide (Aβ) toxicity and tau hyperphosphorylation are hallmarks of Alzheimer’s disease (AD). How their molecular relationships may affect the etiology, progression, and severity of the disease, however, has not been elucidated. We now report that incubation of foetal rat cortical neurons with Aβ up-regulates expression of the Regulator of Calcineurin gene RCAN1, and this is mediated by Aβ-induced oxidative stress. Calcineurin (PPP3CA) is a serine-threonine phosphatase that dephosphorylates tau. RCAN1 proteins inhibit this phosphatase activity of calcineurin. Increased expression of RCAN1 also causes up-regulation of glycogen synthase kinase-3beta (GSK3β), a tau kinase. Thus, incr…
GAL4-responsive UAS- tau as a tool for studying the anatomy and development of the Drosophila central nervous system
1997
To improve the quality of cytoplasmic labelling of GAL4-expressing cells in Drosophila enhancer-trap and transgenic strains, a new GAL4-responsive reporter UAS-tau, which features a bovine tau cDNA under control of a yeast upstream activation sequence (UAS), was tested. Tau, a microtubule-associated protein, is distributed actively and evenly into all cellular processes. Monoclonal anti-bovine Tau antibody reveals the axonal structure of the labelled cells with detail similar to that of Golgi impregnation. We demonstrate that the UAS-tau system is especially useful for studying processes of differentiation and reorganisation of identified neurones during postembryonic development.
Curcumin-derived pyrazoles and isoxazoles: Swiss army knives or blunt tools for Alzheimer's disease?
2007
Curcumin binds to the amyloid beta peptide (Abeta) and inhibits or modulates amyloid precursor protein (APP) metabolism. Therefore, curcumin-derived isoxazoles and pyrazoles were synthesized to minimize the metal chelation properties of curcumin. The decreased rotational freedom and absence of stereoisomers was predicted to enhance affinity toward Abeta(42) aggregates. Accordingly, replacement of the 1,3-dicarbonyl moiety with isosteric heterocycles turned curcumin analogue isoxazoles and pyrazoles into potent ligands of fibrillar Abeta(42) aggregates. Additionally, several compounds are potent inhibitors of tau protein aggregation and depolymerized tau protein aggregates at low micromolar …
Diabetes and cognitive decline
2022
Epidemiologic studies have documented an association between diabetes and increased risk of cognitive decline in the elderly. Based on animal model studies, several mechanisms have been proposed to explain such an association, including central insulin signaling, neurodegeneration, brain amyloidosis, and neuroinflammation. Nevertheless, the exact mechanisms in humans remain poorly defined. It is reasonable, however, that many pathways may be involved in these patients leading to cognitive impairment. A major aim of clinicians is identifying early onset of neurologic signs and symptoms in elderly diabetics to improve quality of life of those with cognitive impairment and reduce costs associa…
Aβ and tau toxicities in Alzheimer’s are linked via oxidative stress-induced p38 activation: Protective role of vitamin E
2014
AbstractOxidative stress is a hallmark of Alzheimer’s disease (AD). We propose that rather than causing damage because of the action of free radicals, oxidative stress deranges signaling pathways leading to tau hyperphosphorylation, a hallmark of the disease. Indeed, incubation of neurons in culture with 5 µM beta-amyloid peptide (Aβ) causes an activation of p38 MAPK (p38) that leads to tau hyperphosphorylation. Inhibition of p38 prevents Aβ-induced tau phosphorylation. Aβ-induced effects are prevented when neurons are co-incubated with trolox (the water-soluble analog of vitamin E).We have confirmed these results in vivo, in APP/PS1 double transgenic mice of AD. We have found that APP/PS1 …
Physical exercise in the prevention and treatment of Alzheimer's disease
2020
Highlights • Low levels of physical activity are a risk factor associated with Alzheimer's disease. • Older adults who exercise are more likely to maintain cognition. • Exercise modulates amyloid β turnover, inflammation, synthesis, and release of neurotrophins, and cerebral blood flow.