Intensive protein synthesis in neurons and phosphorylation of beta-amyloid precursor protein and tau-protein are triggering factors of neuronal amyloidosis and Alzheimer's disease

Abstract

Recently the studies of Alzheimer’s disease have become particularly actual and have attracted scientists from all over the world to this problem as a result of dissemination of this dangerous disorder. The reason for such pathogenesis is not known, but the final image, for the first time obtained on microscopic brain sections from patients with this disease more than a hundred years ago, is well known to clinicists. This is the deposition of Ab amyloid in the brain tissue of senile plaques and fibrils. Many authors suppose that the deposition of beta-amyloid provokes secondary neuronal changes which are the reason of neuron death. Other authors associate the death of neurons with hyperphosphorylation of tau-proteins which form neurofibrillar coils inside nerve cells and lead to their death. For creation of methods of preclinical diagnostics and effective treatment of Alzheimer’s disease novel knowledge is required on the nature of triggering factors of sporadic isoforms of Alzheimer’s disease, on cause-effect relationships of phosphorylation of amyloid precursor protein with formation of pathogenic beta-amyloids, on the relationship with these factors of hyperphosphorylation of tau-protein and neuron death. In this review we analyze the papers describing the increasing of intensity of biosynthesis in neurons in normal conditions and under the stress, the possibility of development of energetic unbalanced neurons and activation of their protective systems. Phosphorylation and hyperphosphorylation of tau-proteins is also tightly connected with protective mechanisms of cells and with processes of evacuation of phosphates, adenosine mono-phosphates and pyrophosphates from the region of protein synthesis. Upon long and high intensity of protein synthesis the protective mechanisms are overloaded and the complementarity of metabolitic processes is disturbed. This results in dysfunction of neurons, transport collapse, and neuron death.

Ischemia‐modified albumin and advanced oxidation protein products as potential biomarkers of protein oxidation in Alzheimer's disease

“…The main pathological features of AD are the extracellular deposition of amyloid β peptide into plaques, and the formation of intracellular tangles composed of the hyperphosphorylated Tau protein . Several molecular pathways have been implied in the progression of AD.…”

Changes in the activity of lysosomal cysteine proteases of plasma mononuclear and polymorphonuclear blood leukocytes in Alzheimer’s disease

“…Последовательное расщепление белка альфа-и гамма-секретазой приводит к формированию пептидов р3 (неамилоидогенный путь). В случае альтернативного процессинга с помощью бета-и гамма-секретазы образуется полипептид, состоящий из 40-43 аминокислотных остатков (β-амилоид), нерастворимый в воде, агрегирующий с образованием полимеров, откладывающихся в виде бляшек [7].…”

Anti-Cytokine Activity of Curcumin and Its Binding to a Fragment of AβPP

“…In particular, several studies have shown that Aβ accumulates abundantly in certain brain areas namely, hippocampus and cerebral cortex which subserve information acquisition and processing, and memory [5][6][7]. This peptide is formed within the amyloyidogenic processing of the amyloid-β protein precursor (AβPP) [8][9][10].…”