According to a recent study, a type of drug designed for cancer treatment showed potential as a new treatment for neurological illnesses such as Alzheimer’s. Researchers uncovered an enzyme that affects glucose metabolism in the brain, as well as the possibility that a cancer treatment could help treat early-stage Alzheimer’s.
Aging and neurodegenerative disorders are believed to affect glucose metabolism in the brain. Scientists have discovered an enzyme that controls alterations in the brain’s glucose metabolism that result from diseases like Alzheimer’s and Parkinson’s.
Researchers discovered that inhibiting the enzyme indoleamine-2,3-dioxygenase 1, or IDO1, preserved memory and cognition in the early disease stages in a mouse model of Alzheimer’s.
They observed that an immunotherapy cancer medicine might inhibit this pathway, restoring function to the afflicted brain regions. Science published the research findings [1].
IDO1 inhibitors are currently underway to treat a variety of cancers, including melanoma, leukemia, and breast cancer. According to researchers, their discoveries might expedite the distribution of these drugs and allow for their repurposing as early-stage treatments for neurodegenerative illnesses [2].
An Enzyme Could Help Slow Alzheimer’s Progression.
Researchers from Penn State, Stanford University, Princeton University, Salk Institute, and Kyoto University. Investigated how an enzyme in astrocytes affected neuron communication in the hippocampus, the brain region involved in memory and learning.
Lactate fuels neurons in the brain, and the chemical kynurenine regulates its production. IDO1 is an enzyme that converts the amino acid tryptophan (TRP) into kynurenine (KYN). KYN is linked to brain aging and neurodegenerative diseases.
The metabolites produced by this conversion are involved in the immune regulation. The researchers have previously studied this pathway. This time, however, they focused on the IDO1 enzyme.
Initially, the team was studying the immunological mechanisms behind brain injury. Later, they decided to investigate an inflammatory route linked to prostaglandin E2.
Examining the conversion of TRP into KYN, they discovered that in a mouse model of Alzheimer’s. The enzyme IDO1, which controls this metabolic route, reacted in a different way than expected.
According to the corresponding author, Katrin Andreasson, MD, Stanford University professor of neurology and neurological sciences. They examined the role they hypothesized IDO1 would play in a mouse model of amyloid buildup, but the results were entirely unexpected. That naturally aroused their interest, so they dug deeper and discovered that this pathway was critical in a different cell type, the astrocyte. Not in the immune cells as much. That’s how they focused on astrocytes and their metabolic support for neurons.
A Cancer Drug May Boost Metabolic Activity in the Brain.
Researchers discovered IDO1 activity in astrocytes but not neurons in mice. It implied that the route under investigation occurred solely in these cells.
They proposed that the presence of tau and amyloid beta, two proteins found in Alzheimer’s patients. Would cause an increase in the enzyme IDO1 in astrocytes.
Researchers discovered that upon exposing mouse astrocytes to amyloid beta and tau proteins, the expression of IDO1 genes rose dramatically. They also found that astrocyte glucose metabolism decreased in response to a subsequent rise in KYN.
The findings supported the researchers’ hypothesis that disrupting the homeostasis of this pathway could contribute to the alteration of glucose metabolism found in Alzheimer’s patients.
Further investigations with mice neurons in the lab revealed that PF068, a cancer immunotherapy medication that inhibits IDO1 activity, increased glycolysis and mitochondrial respiration in astrocytes but not neurons in a dose-dependent way.
After giving the cancer medication to Alzheimer’s mice models for a month, the researchers used the maze test to gauge the mice’s memory.
The results demonstrated that the medication could improve mice’s memories. Further investigation of their hippocampus tissues revealed that PF068 inhibited the KYN rise reported in Alzheimer’s mice model with amyloid beta buildup. This shows that the drug’s blockage of this pathway was responsible for rescuing these mice’s memories.
Further studies on human brain tissues, including those from Alzheimer’s patients, revealed a rise in KYN but not TRP among those who had passed away with more severe dementia symptoms.
Additionally, using astrocytes produced from human induced pluripotent stem cells (iPSCs) originating from late-onset Alzheimer patients. Researchers demonstrated that following IDO1 inhibition with PF068, the loss in glucose metabolism was restored.
According to Andreasson, the researchers planned to examine patient-derived astrocytes in the future to dig into this process in younger and older patients and those with various neurological disorders.
Alzheimer’s Research Association is a non-profit organization dedicated to helping caregivers of Alzheimer’s disease and dementia. We provide the latest information and news about the illness and helpful tips to help caregivers cope with their daily caregiving challenges. We realize the most important thing that a caregiver needs is financial assistance. Therefore, we provide grants to caregivers to ease their financial burden. Caregivers can apply for grants here: Alzheimer’s Grant Application.
You can also help caregivers in their endeavor by donating as much as possible: https://www.alzra.org/donate-now/.
