Current Alzheimer Research - Volume 5, Issue 6, 2008

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Neurodegeneration is a complex and multifaceted process leading to many chronic diseased states. Neurodegenerative disorders include a number of different pathological conditions, like Alzheimer's and Parkinson's diseases, which share similar critical metabolic processes, such as protein aggregation, which could be affected by some metal ions. A huge number of reports indicate that, among putative aggravating factors, Read More

The aim of this review is to show how the challenging problem of understanding the physico-chemical basis of protein misfolding and aggregation which are at the origin of plaque formation in amyloid pathologies can be successfully investigated with a combination of modern spectroscopic techniques and advanced first principle numerical simulations. Within the vast group of diseases (more than 20) characterized by extra- Read More

Multiple lines of evidence demonstrate that oxidative stress is an early event in Alzheimer's disease (AD), occurring prior to cytopathology, and therefore may play a key pathogenic role in AD. Oxidative stress not only temporally precedes the pathological lesions of the disease but also activates cell signaling pathways, which, in turn, contribute to lesion formation and, at the same time, provoke cellular responses such a Read More

Alzheimer's disease (AD) is the most common form of dementia in the elderly, and is characterized by the deposition of extracellular amyloid plaques primarily composed of the β-amyloid peptide (Aβ). While these plaques define the pathology of AD, disease progression has been shown to correlate more closely with the level of synaptotoxicity induced by soluble Aβ oligomers. Recent evidence suggests that these oligomers Read More

Amyloid β peptide (Aβ),42-residue peptide and its variations, is known to form amyloid fibrils in Alzheimer's disease. Solid-state NMR study reveals a parallel β-sheet structure in the Aβ fibrils. The atomic level structure of Aβ in aqueous environment, however, has not been determined, because of its tendency to aggregate. There are several reports that soluble forms of Aβ possess intrinsic neurotoxicity. It has recently become pos Read More

It is widely accepted that Aβ42 aggregation is a central event in the pathogenesis of Alzheimer's disease. Aβ42 oligomers and fibrils cause the breakdown of neural circuits, neuronal death and eventually dementia. There are a number of physiological molecules that can protect Aβ42 from aggregation. Promoting such protective molecules and mechanisms against Aβ42 aggregation may be a novel direction in AD drug disc Read More

The amyloid cascade hypothesis is well known hypothesis describing the pathogenesis of Alzheimer's disease (AD). On the basis of this hypothesis, inhibition of amyloid β-protein (Aβ) generation and aggregation, enhancement of extracellular Aβ removal, and Aβ vaccination are currently under investigation. Intracellular Aβ may be even more important than extracellular Aβ, since intraneuronal Aβ accumulation commonly prece Read More

Human post-mortem brain samples are excellent source material for the analysis of age-related disorders such as Alzheimer's disease (AD). Moreover, data obtained from cell culture- or mouse model-related experiments often need to be validated by using human tissue. In a variety of studies over the last few years, a huge list of genes or proteins with differential expression or abundance between AD-related and contr Read More

The PrP propensity to adopt different structures is tightly linked to transmissible spongiform encephalopathies (TSE) which include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scjeinker (GSS) and Kuru syndrome. In most cases, TSE is associated with the accumulation in the brain of an abnormally folded protease-resistant protein, PrPSc or PrPres, which is derived from a cellular host-encoded protease-sensitive conform Read More

Prion diseases are fatal neurodegenerative disorders related to the conformational alteration of the prion protein (PrPC) into a pathogenic and protease-resistant isoform PrPSc. PrPC is a cell surface glycoprotein expressed mainly in the central nervous system and despite numerous efforts to elucidate its physiological role, the exact biological function remains unknown. Many lines of evidences indicate that prion is a copper Read More

Intracellular accumulation of filamentous tau proteins is a defining feature of neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and frontotemporal dementia with Parkinsonism linked to chromosome 17, all known collectively as tauopathies. Tau protein is a member of microtubule (MT)-associated proteins. Tau is a highly soluble and na Read More

A number of studies have demonstrated a role for transition metals and oxidative stress in the etiology of Parkinson’s disease (PD). Genetic and biochemical evidence also clearly links the protein alpha-synuclein (αSyn) to PD and a number of associated diseases. In these “synucleinopathies”, αSyn is deposited, often in oligomerized forms, as cytoplasmic inclusions known as Lewy bodies and Lewy neurites. αSyn cross-linking/oli Read More