Saturday , November 28 2020

New information on the pathological mechanisms of Alzheimer's disease

The researchers reported that pathological tau accumulation triggered a safety valve mechanism in well-regulated cell membranes Araştırma


Alzheimer's disease is associated with two neuropathologies: amyloid plaques and tau aggregates or tau protein accumulated in neurofibrillary tangles in neurons. Brain amyloid plaques are better known pathology, but the importance of tau to disease progression is equally important.

IF In Alzheimer's disease, amyloid deposition in the brain is the first to begin, but the amyloid pathology typically shows symptoms after inducing tau pathology. At this point, neuronal cell death and loss of synapses are accelerating, am says Henri Huttunen at the Neuroscience Center of Helsinki University (a HiLIFE). unit of).

”Tau accumulation seems to be a really harmful element of the disease.“

Tau is also seen in healthy neurons, but incorrectly folded, pathological tau accumulation plays an important role in Alzheimer's.

Previously, it was thought that tau aggregates would only gain access from outside the cells after death of the cells, but in recent years tau pathology has been found to pass from the patient to healthy cells. However, before this, the molecular mechanisms that help tau cells penetrate are not understood.

The latest study by Henri Huttunen and Riikka-Liisa Uronen's research group shows that pathological tau accumulation triggers a safety valve mechanism in well-regulated cell membrane.

T As the regulatory mechanisms of the tau protein increase, the protein ends in the cell membrane in the cell cell skeleton. Huttunen demonstrates that the cholesterol-rich lipid shells of the cell membrane play a central role in this tau secretion mechanism.

The study used cultured neurons and adapted reporter proteins to closely monitor tau transfer between cells.

Normally, the cell membrane keeps the inner and outer parts of the cell completely separate. The membrane is an oil film with permeability that is carefully regulated to proteins, neurotransmitters and other biomolecules.

From the perspective of drug development, a new mechanism for targeting pharmacological molecules is presented. The accumulation of tau and amyloid into the cerebrospinal fluid and brain is already used in the diagnosis of the disease.

Molecular data on how Tau interacts with cell membranes can potentially be used to slow Alzheimer's disease and other diseases associated with a group known as tauopathies.

Unlike amyloid plaques, tau protein aggregates also occur in other neurodegenerative diseases such as frontotemporal dementia.

"We are currently only able to treat the symptoms of these diseases, which makes the development of a treatment slowing disease progression an important goal," says Huttunen.

The Huttunen-managed project observed that cell membranes are sensitive to manipulation and that omega-3 fatty acids are particularly effective in preventing the membrane from penetrating.

Neuronal cell membranes contain much more omega-3 fatty acids than other cell types, and there are epidemiological data that give importance to brain health reflected in current dietary recommendations.

Sal When omega-3 fatty acid DHA was added to cell cultures, tau secretion from cells collapsed. Hegunen modifies the microstructure of omega-3 fatty acids to make the cell membrane less permeable for tau aggregates, which captures the protein within the cell, He says Hegunen.

Working published Cell Reports magazine.

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