Studies of
neurodegenerative disorders (NDDs) are drawing more attention of researchers worldwide due to the high incidence of
Alzheimer's disease (AD). The pathophysiology of such disorders is, in part, characterized by the transition of a wild-type
peptide from its native conformation into a very stable pathological
isoform. Subsequently, these abnormal
proteins form aggregates of
amyloid fibrils that continuously increase in size. Changes in the metabolic processes of neurons (e.g. oxidative stress, hyperphosphorylation of the
tau protein, and resulting secondary changes in the cell metabolism) ultimately lead to cell death. We hypothesize that extracellular deposition of β-
amyloid peptide fibrils and neurofibrillary tangles represents the body's adaptation mechanism, aimed at preservation of autonomic functioning; while the
cognitive decline is severe, the rest of the organ systems remain unaffected and continue to function. This hypothesis is supported by the fact that destruction of pathological plaques, fibrils, and tangles and the use of
vaccines targeting β-
amyloid result in undesirable side effects. To gain a better understanding of the pathophysiology of
Alzheimer's disease and to develop novel
therapies, continued studies of the sporadic form of disease and the mechanisms triggering conformational changes in β-
amyloid peptide fragments are essential. This review is focused on studies investigating the formation of
amyloid fibrils and their role in the pathogenesis of
neurodegenerative diseases. In addition, we discuss a related disorder--
amyloidosis--where formation of fibrils, tangles, and plaques leads to neuronal death which may occur as a result of a failed adaptation process. Further in-depth investigation and comprehensive analysis of alterations in the metabolism of APP, β-
amyloid, and
tau protein, which have a pathological effect on cell membrane, alter
phosphate exchange, and impair other key metabolic functions of the cell long before the characteristic
amyloid deposition takes place, is warranted. A better understanding of intraneuronal processes is crucial in identifying specific inhibitors of pathologic neuronal processes and, consequently, will allow for targeted
therapy, thus maximizing efficacy of selected therapeutic regimens.