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March 2012 - May 2019
Publications
Publications (30)
The identification of compounds which protect the double-membrane of mitochondrial organelles from disruption by toxic confomers of amyloid proteins may offer a therapeutic strategy to combat human neurodegenerative diseases. Here, we exploited an extract from the marine brown seaweed Padina pavonica (PPE) as a vital source of natural bioactive com...
Abstract Studies on the amyloidogenic N-terminal domain of the E. coli HypF protein (HypF-N) have contributed significantly to a detailed understanding of the pathogenic mechanisms in neurodegenerative diseases characterised by the formation of misfolded oligomers, by proteins such as amyloid-β, α-synuclein and tau. Given that both cell membranes a...
INTRODUCTION: Given the centrality of mitochondrial dysfunction in neurodegenerative diseases, the aim of this study was to address the formation of channel-like pores in mito-mimetic lipid bilayers by oligomeric species of the amyloidogenic α-synuclein and tau proteins. METHODOLOGY: Oligomers were prepared as described[1]. Formation of single chan...
Misfolding and aggregate formation by the tau protein has been closely related with neurotoxicity in a large group of human neurodegenerative disorders, which includes Alzheimer's disease. Here, we investigate the membrane-active properties of tau oligomers on mitochondrial membranes, using minimalist in vitro model systems. Thus, exposure of isola...
Aggregation of the amyloid-forming α-synuclein (αS) protein is closely associated with the etiology of Parkinson’s disease (PD), the most common motor neurodegenerative disorder. Many studies have shown that soluble aggregation intermediates of αS, termed oligomers, permeabilize a variety of phospholipid membranes; thus, membrane disruption may rep...
In the Maltese Islands, the proportion of individuals aged 65 years and over is expected to increase significantly in the coming decades, placing significant burdens on healthcare and support services. One example of a costly consequence of ever-longer life expectancy is the increase in people with dementia, especially Alzheimer’s disease. The agei...
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Alzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally befor...
A signature feature of neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer’s disease (AD) and α synuclein (α-syn) in Parkinson’s disease (PD), into soluble oligomeric structures that are highly neurotoxic. We investigated whether extracts derived from two ubiquitous Mediterranean pl...
A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer’s disease (AD) and α-synuclein (α-syn) in Parkinson’s disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark...
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common age-related neurodegenerative disorders and hence pose remarkable socio-economical burdens to both families and state. Although AD and PD have different clinical and neuropathological features, they share common molecular mechanisms that appear to be triggered by multi-factor...
Parkinson's disease (PD) is a common motor neurodegenerative disorder with multifactorial etiology that is an increasing burden on our aging society. PD is characterized by nigrostriatal degeneration which might involve oxidative stress, α-synuclein (αS) aggregation, dysregulation of redox metal homeostasis and neurotoxicity. Although the exact cau...
This edited volume concerns a group of devastating neurological disorders that share a common pathological mechanism, namely the aggregation and deposition of insoluble, proteinaceous lesions, termed ‘amyloid’. Examples of cerebral amyloid disorders include common neurodegenerative diseases like Alzheimer’s disease-related dementia and Parkinson’s...
Alzheimer and Parkinson diseases are age-related neurodegenerative disorders in which formation of amyloid aggregates by amyloid-beta (Abeta) and α-synuclein (αS) proteins, respectively, are recognised critical events that occur early in the disease process. These aggregates cause disruption of mitochondrial function in neurons, initiating a pathop...
Alzheimer's disease and Parkinson's disease are neurodegenerative disorders characterized by the misfolding of proteins into soluble prefibrillar aggregates. These aggregate complexes disrupt mitochondrial function, initiating a pathophysiological cascade leading to synaptic and neuronal degeneration. In order to explore the interaction of amyloid...
BACKGROUND: The pathophysiology of Parkinson’s disease, the most common motor neurodegenerative disorder, is thought to involve oligomerization of the protein alpha-synuclein (αS) and mitochondria-induced apoptosis of dopaminergic neurons in the nigrostriatal pathway.
OBJECTIVES: The aim of the study was to screen 13 small-molecule polyphenolic com...
Cumulative evidence now suggests that the abnormal aggregation of the protein α-synuclein (αS) is a critical factor in triggering neurodegeneration in Parkinson's disease (PD). In particular, a fundamental pathogenetic mechanism appears to involve targeting of neuronal membranes by soluble oligomeric intermediates of αS, leading to their disruption...
Aggregation of α-synuclein is involved in the pathogenesis of Parkinson's disease (PD). Studies of in vitro aggregation of α-synuclein are rendered complex because of the formation of a heterogeneous population of oligomers. With the use of confocal single-molecule fluorescence techniques, we demonstrate that small aggregates (oligomers) of α-synuc...
Amyloid-β (Aβ) aggregation is a recognized key process in the pathogenesis of Alzheimer's disease (AD). Misfolded Aβ peptides self-assemble into higher-order oligomers that compromise membrane integrity, leading to synaptic degeneration and neuronal cell death. The main aim of this study was to explore whether small-molecule compounds and black tea...
Aggregation of alpha-synuclein (αS) into oligomers is critically involved in the pathogenesis of Parkinson's disease (PD). Using confocal single-molecule fluorescence spectroscopy, we have studied the effects of 14 naturally-occurring polyphenolic compounds and black tea extract on αS oligomer formation. We found that a selected group of polyphenol...
Cumulative evidence now suggests that the abnormal aggregation of the neuronal protein alpha-synuclein is critically involved in the pathogenesis of synucleinopathies, of which Parkinson's disease (PD) is the most prevalent. Development of neuropathology appears to be linked to events that accelerate the rate of aggregation of alpha-synuclein from...
Aims: Parkinson’s disease (PD) is the most common motor
disorder and the second most common neurodegenerative disease.
Cumulative evidence now suggests that the aggregation of alpha-
synuclein (aS) is critically involved in the pathogenesis of PD. The
main aim of our research is to show that natural polyphenolic
compounds are strong inhibitors...
Nutrition management is considered to be a cornerstone of therapy for patients with diabetes mellitus (DM). The prevalence of DM is increasing around the world at such a dramatic rate to be characterized as an epidemic. Many factors have been postulated to contribute to the DM epidemic. This paper discusses nutritional recommendation related to the...
Overweight and obesity is becoming epidemic, worldwide, in both adults
and children. This problem is particularly evident in all most all westernised
societies due to particular lifestyle and dietary habits. 20% of Europe’s
school-age children are estimated to be overweight and of these, 1 in 5 is
obese. The local situation is reaching critical...