Anti-cancer drugs can treat Alzheimer’s in its early stages

2024-08-22 18:00:05

A family of drugs developed to treat cancer may also have an effect on neurodegenerative diseases, such as Alzheimer’s.

Among the many ways Alzheimer’s disease can affect brain function is the alteration of glucose metabolismimportant to contribute to mental health. In particular, impaired metabolism destroys brain power, affecting thinking and memory.

Research published in ‘Knowledge‘ analyzed a critical regulator of brain metabolism known as the kynurenine pathway. The intervention of researchers Penn State University and the Stanford University (USA) is that way kynurenine It is hyperactivated as a result of amyloid plaque and tau proteins that accumulate in the brains of patients with Alzheimer’s disease.

The work showed that by blocking a specific enzyme called indole-2,3-dioxygenase 1, or IDO1 for short, they could recover memory and brain function in Alzheimer’s disease-related models.

The findings suggest that IDO1 inhibitors currently being developed as a treatment for several types of cancer, including melanoma, leukemia and breast cancer, could be adapted to treat the early stages of neurodegenerative diseases, the first for chronic diseases that have no treatment. barrier

“We have shown that there is great potential for IDO1 inhibitors, which are already among the drugs that are being developed for cancer treatments, to be targeted in the treatment of Alzheimer’s,” he said. Melanie McReynolds co-author of the article.

“We were surprised that these metabolic improvements were so effective not only in preserving healthy synapses, but also in rescuing behavior. “Mice performed better on cognitive and memory tests when administered drugs that block the kynurenine pathway,” admits the lead author. Katrin Andreassonlead author of the study’s research.

Andreasson explained that “blocking this enzyme, especially with compounds that have already been discovered in human clinical trials for cancer, could be a big step forward in finding ways to protect our brain from the damage caused by aging and neurodegeneration.”

Alzheimer’s disease affects the parts of the brain that control thinking, memory and language, as a result of the progressive and irreversible loss of synapses and neuronal circuits. As the disease progresses, symptoms can range from mild memory loss to the loss of the ability to communicate and respond to the environment. Current treatments for the disease focus on controlling symptoms and slowing progression, by acting on the accumulation of amyloid and tau plaques in the brain, but there are no approved treatments to combat the onset of the disease.

“Scientists are working on the side effects of what we identify as a problem with the way the brain feeds itself,” he said. Praveena Prasadco-author of the article. “Therapies available are aimed at removing peptides that may be the result of a serious problem that can be addressed before those peptides can start to form plaques. “Now, we have shown that by talking about brain production, we can not only slow down, but reverse the progression of this disease.”

Alzheimer’s models

Using preclinical models (in vitro cell models with amyloid and tau proteins, in vivo mouse models, and in vitro human cells from Alzheimer’s patients), they showed that inhibiting IDO1 helps to restore the glucose production of health in astrocytes, star-shaped brain cells that provide. metabolic support to neurons.

The researchers conducted the study in several models of Alzheimer’s disease, specifically amyloid or tau accumulation, and found that the protective effects of blocking IDO1 extend to these two different mechanisms.

Their findings suggest that IDO1 may also be important in cancers with other types of pathology, viz Parkinson’s disease dementiaas well as the broad spectrum of progressive neurodegenerative disorders known as tauopathies, explained Paras Minhas, first author of the article.

“The brain relies heavily on glucose to activate many processes, so losing the ability to use glucose effectively for energy production and metabolism can lead to metabolic dysfunction and, in particular, cognitive impairment,” said Minhas. “Through this collaboration we are able to visualize exactly how brain structure is affected by neurodegeneration.”