The role of autophagy in beta-amyloid secretion

Autophagy is responsible for the secretion of beta-amyloid

LifeSciencesToday based on RIKEN materials: Cell auto-cleaning mechanism mediates the formation of plaques in Alzheimer'sAutophagy, a key cellular mechanism of self-purification, mediates the formation of beta–amyloid plaques – one of the signs of Alzheimer's disease - and may be a potential target of drugs for the treatment of this disease.

This is the conclusion from a new study by a group of scientists from the RIKEN Brain Science Institute, Japan. The work sheds light on the metabolism of beta-amyloid and its role in neurodegeneration and memory loss.

Doctors Per Nilsson, Takaomi Saido and their colleagues, who published a report on their experiments on transgenic mice in the journal Cell Reports (Abeta Secretion and Plaque Formation Depend on Autophagy), for the first time showed that the absence of autophagy in neurons prevents the secretion of beta-amyloid and the formation of beta-amyloid plaques in the brain. In addition, the study proved that the accumulation of beta-amyloid inside neurons is toxic to cells.

Alzheimer's disease, the most common form of dementia, affects almost 36 million people worldwide, and this number is expected to double over the next 20 years. However, the causes of the disease are not fully understood and even symptomatic therapy has not been developed today.

In the brains of patients with Alzheimer's disease, beta-amyloid levels are elevated and beta-amyloid plaques form in the interneuronal space. This accumulation of beta-amyloid leads to the death of neurons, but the mechanism determining the exact cause of cell death has remained a mystery until now. It was not known what causes the greatest harm to neurons – increased intracellular levels of beta-amyloid or deposition of a peptide in the form of plaques in the interstitial space.

Autophagy is a mechanism for removing protein aggregates and other biochemical "garbage" from a cell, and this process is disrupted to a certain extent in Alzheimer's disease.

The role of autophagy in the secretion of beta-amyloid by neurons (Fig. Cell Reports)To study the role of autophagy in beta-amyloid metabolism, Dr. Nilsson and his colleagues blocked an important autophagy gene, Atg7, in mice with an Alzheimer's disease model.

Contrary to what was expected, the results of these experiments showed that the complete absence of autophagy inside the neurons prevents the formation of beta-amyloid plaques outside the cells. Instead, beta-amyloid accumulates inside neurons, causing their death, which in turn leads to memory loss.

The secretion of beta-amyloid by neurons depends on autophagy. In the picture: neurons of a wild-type mouse (wt) and mice of the Atg7flox/flox line with impaired autophagy. Violation of autophagy dramatically reduced the load of extracellular beta-amyloid plaques caused by suppression of beta-amyloid secretion, which led to its abnormal intra-neuronal accumulation in the perinuclear region. (Photo: Per Nilsson, RIKEN)"Our study explains how neurons secrete beta-amyloid through autophagy, which was not entirely clear," Dr. Nilsson commented on his study.

"Controlling the metabolism of beta-amyloid, including its secretion, is the key to fighting this disease. Therefore, autophagy may be a potential target of drugs for the treatment of Alzheimer's disease."

Portal "Eternal youth" http://vechnayamolodost.ru06.11.2013