Endocytosis versus beta-amyloid

Molecular Pathway Found to Stop Alzheimer's Disease

Sergey Kolenov, Hi-tech+

Researchers from the United States have discovered a pathway that prevents the accumulation of a toxic form of beta-amyloid proteins – one of the main causes of Alzheimer's disease. Scientists have protected mice, it remains only to understand how to activate this mechanism in humans.

Experts from St. Jude Children's Research Hospital have discovered a molecular mechanism that prevents the accumulation of toxic proteins in the brain responsible for the symptoms of Alzheimer's disease. As noted in the press release, the discovery will also regulate inflammation and the immune response against malignant brain tumors.

A molecular pathway called LC3-associated endocytosis (LC3-associated endocytosis, LANDO) has been identified in microglia – immune cells of the central nervous system.

During experiments with mice, scientists have proved that its activation protects against the accumulation of a toxic form of beta-amyloid protein, as well as neuroinflammation and neurodegeneration.

Scientists compare the operation of this system with a car wash. Microglial receptors capture improperly folded beta-amyloid proteins and deliver them for disposal. Then they return to the surface of the immune cell. The proteins Rubicon, Beclin 1, ATG5 and ATG7 are necessary for the molecular pathway to work correctly.

Figure from the article Bradlee et al. LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer's Disease, published in the journal Cell – VM.

With age, their expression decreases, which may be one of the causes of neurodegenerative diseases.

According to the researchers, the activation of LC3-associated endocytosis can become the basis for the therapy of Alzheimer's disease due to the destruction of toxic beta-amyloids and the mitigation of neuroinflammation. At the same time, in children with a brain tumor, it is more logical to inhibit this pathway, so that microglia will more actively destroy cancer cells.

Parkinson's disease is another disease associated with the accumulation of improperly folded proteins. New data confirm that toxic alpha-synucleins can occur in the intestine, and then spread along the vagus nerve to the brain and destroy it.

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