Current Alzheimer Research - Volume 5, Issue 3, 2008

Alzheimer's disease is clearly one of the most important human disorders of the 21st century. With the increasing life expectancy, the rapidly growing prevalence of this disease will obviously bear profound social and economical implications, in addition to the medical ones. Therefore, understanding the etiology of Alzheimer's disease is a challenging yet very important task, which will likely open new venues toward ther Read More

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the growing population of elderly people. A characteristic of AD is the accumulation of plaques in the brain of AD patients, and theses plaques mainly consist of aggregates of amyloid β-peptide (Aβ). All converging lines of evidence suggest that progressive accumulation of the Aβ plays a central role in the genesis of Alzheimer's disease and it was long un Read More

Self-assembly of the 40/42 amino acid Aβ peptide is a key player in Alzheimer's disease. Aβ40 is the most prevalent species, while Aβ42 is the most toxic. It has been suggested that the amino acids 21-30 could nucleate the folding of Aβ monomer and a bent in this region could be the rate-limiting step in Aβ fibril formation. In this study, we review our current understanding of the computer-predicted conformations of amino Read More

The proteins Ure2, Sup35 and Rnq1 from the baker's yeast have infectious properties, termed prions, at the origin of heritable and transmissible phenotypic changes. It is widely believed that prion properties arise from the assembly of Ure2p, Sup35p and Rnq1p into insoluble fibrils. Yeast prions possess regions crucial for their propagation that can be either N- or C-terminal. These regions have unusual amino acid composi Read More

Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation, which shares many structural properties with the pre-molten globule state, a partially folded intermediate first found duri Read More

Targeting the initial formation of amyloid assemblies is a preferred approach to therapeutic intervention in amyloidoses, which include such diseases as Alzheimer's, Parkinson's, Huntington's, etc., as the early-stage, oligomers that form before the development of β-conformation-rich fibers are thought to be toxic. X-ray patterns from amyloid assemblies always show two common intensity maxima: one at 4.7 Å corresp Read More

Amyloid fibrils are elongated protein aggregates well known for their association with many human diseases. However, similar structures have also been found in other organisms and amyloid fibrils can also be formed in vitro by other proteins usually under non-physiological conditions. In all cases, these fibrils assemble in a nucleated polymerization reaction with a pronounced lag phase that can be eliminated by supplying pr Read More

Several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's and prion diseases, are characterized pathognomonically by the presence of intra- and/or extracellular lesions containing proteinaceous aggregates, and by extensive neuronal loss in selective brain regions. Related non-neuropathic systemic diseases, e.g., lightchain and senile systemic amyloidoses, and other organ-specific diseases, such as Read More

Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients, and its prevalence is expected to soar in coming decades. Neuropathologically, AD is characterized by beta-amyloid-containing plaques, tau-containing neurofibrillary tangles, and cholinergic neuronal loss. In addition to the hallmark of memory loss, the disease is associated with other neuropsychiatric and behavioral abnorma Read More