New U.S. study reveals pathogenesis of neurodegenerative diseases

Mondo Health Updated on 2024-02-27

BEIJING, Feb. 27 (Xinhua) -- A new U.S. study has found that plaque deposition in the brain is not the direct cause of killing brain cells, but it can interfere with the mechanism of brain cell stress response, and the sustained stress response is the culprit that causes brain cell death.

Many neurodegenerative diseases, such as Alzheimer's disease, have protein plaque deposition in the brain as the main pathological feature, but to date, the focus on breaking down and removing protein plaques in the brain has had little effect.

According to a recent press release issued by the University of California, Berkeley, researchers from Stanford University have found that a supermolecular protein complex called "Integrated Stress Response Silencing Factor (SIFI)" plays an important role in the pathogenesis of a variety of neurodegenerative diseases.

This protein complex has two functions, namely clearing the brain of the accumulation of protein plaques and shutting down the brain cell stress response triggered by the accumulation of protein plaques. When there is an abnormal accumulation of protein plaques in brain cells, the stress response of brain cells regulated by SIFI will be turned on to remove the plaques. And when the plaque is cleared, SIFI shuts down the brain cell stress response. The researchers likened the process to "cleaning the room" and "turning off the lights before going to bed."

Researchers have found mutations in certain components of SIFI in neurodegenerative disease models such as ataxia and early-onset dementia. During the onset of these diseases, the accumulation of protein plaques "hijacks" the silencing mechanism of the brain cell stress response regulated by SIFI, shuts the mechanism by interfering, and the brain cells experience a sustained stress response and eventually die. That is, "[protein] deposits do not directly kill brain cells, they keep the lights on and cause brain cells to die".

The study also found that in a mouse model of early-onset dementia, the use of a drug that shuts down the stress response of brain cells helped brain cells survive. Related** has been published in a recent issue of the British journal Nature.

Researchers believe that many neurodegenerative diseases characterized by protein plaque deposition may have similar pathogenesis, which means that shutting down the brain cell stress response through drugs is expected to be a new strategy for a variety of neurodegenerative diseases.

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