PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Drugs that improve brain metabolism could help Alzheimer’s patients

2024-08-22
(Press-News.org) Among the many ways neuroscientists think Alzheimer’s disease may strip away brain function is by disrupting the glucose metabolism needed to fuel the healthy brain. In essence, declining metabolism robs the brain of energy, impairing thinking and memory.

Against that backdrop, a team of neuroscientists at the Knight Initiative for Brain Resilience at Stanford’s Wu Tsai Neurosciences Institute have zeroed in on a critical regulator of brain metabolism known as the kynurenine pathway. They hypothesize that that the kynurenine pathway is overactivated as a result of amyloid plaque and tau proteins that accumulate in the brains of patients with Alzheimer’s disease.

Now, with support from research and training grants from the Knight Initiative, they have shown that by blocking the kynurenine pathway in lab mice with Alzheimer’s Disease, they can improve, or even restore, cognitive function by reinstating healthy brain metabolism.

“We were surprised that these metabolic improvements were so effective at not just preserving healthy synapses, but in actually rescuing behavior. The mice performed better in cognitive and memory tests when we gave them drugs that block the kynurenine pathway,” said senior author, Katrin Andreasson, a neurologist at the Stanford School of Medicine and member of the Wu Tsai Neurosciences Institute.

The study, which included collaborations with researchers at the Salk Institute for Biological Studies, Penn State University, and others, appeared August 22, 2024 in the journal Science.

Hungry neurons

In the brain, kynurenine regulates production of the energy molecule lactate, which nourishes the brain’s neurons and helps maintain healthy synapses. Andreasson and her fellow researchers specifically looked at the enzyme indoleamine-2,3-dioxygenase 1 — or IDO1, for short  — which generates kynurenine. Their hypothesis was that increases in IDO1 and kynurenine triggered by accumulation of amyloid and tau proteins would disrupt healthy brain metabolism and lead to cognitive decline.

“The kynurenine pathway is over activated in astrocytes, a critical cell type that metabolically supports neurons.  When this happens, astrocytes cannot produce enough lactate as an energy source for neurons, and this disrupts healthy brain metabolism and harms synapses” Andreasson said. Blocking production of kynurenine by blocking IDO1 restores the ability of astrocytes to nourish neurons with lactate.

Best of all for Andreasson, and for Alzheimer’s patients, IDO1 is well known in oncology and there are already drugs in clinical trials to suppress IDO1 activity and production of kynurenine. That meant Andreasson could circumvent the time-intensive work of identifying new drugs and to begin testing in lab mice almost immediately.

In those tests, in which mice with Alzheimer’s Disease must navigate an obstacle course before and after drug intervention, Andreasson and team found that the drugs improved hippocampal glucose metabolism, corrected deficient astrocytic performance, and improved the mice’s spatial memory.

Promise kept

“We also can’t overlook the fact that we saw this improvement in brain plasticity in mice with both amyloid and tau mice models. These are completely different pathologies, and the drugs appear to work for both,” Andreasson noted. “That was really exciting to us.”

Better yet, this intersection between neuroscience, oncology, and pharmacology could help speed drugs to market if proved effective in ongoing human clinical trials for cancer.

“We’re hopeful that IDO1 inhibitors developed for cancer could be repurposed for treatment of AD,” Andreasson stressed.

The next step is to test IDO1 inhibitors in human Alzheimer’s patients to see if they show similar improvements in cognition and memory. Prior clinical tests in cancer patients tested the effectiveness of IDO1 inhibitors on cancer but did not anticipate or measure improvements in cognition and memory. Andreasson is hoping to  investigate IDO1 inhibitors in human trials for Alzheimer’s disease in the near future.

 

Acknowledgements:

Stanford Wu Tsai Neurosciences Institute / Knight Initiative for Brain Resilience authors:

Paras S. Minhas (co-lead), Amira Latif-Hernandez (co-lead), Aarooran S. Durairaj, Qian Wang, Siddhita D. Mhatre, Takeshi Uenaka, Joshua Crapser, Travis Conley, Hannah Ennerfelt, Yoo Jin Jung, Yeonglong Albert Ay, Matthew Matrongolo, Edward N. Wilson, Tao Yang, Marius Wernig, Frank M. Longo, and Katrin I. Andreasson (corresponding).

Other Contributing Institutions

The Salk Institute for Biological Studies (including co-lead author Jeffrey R. Jones), Keio University, Princeton University, Penn State University, UC San Francisco, and the Banner Sun Research Institute.

Wu Tsai Neurosciences Institute / Knight Initiative for Brain Resilience support:

The research was supported by an Innovation Award and a Brain Resilience Scholar Award from the Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute. The study made use of Wu Tsai Neurosciences Institute Community Laboratories: the Stanford Behavioral and Functional Neuroscience Laboratory and the Stanford Neuroscience Microscopy Service, as well as the Stanford Mass Spectroscopy Core.

Competing interests:

Andreasson is a co-founder, board member, and consultant for Willow Neuroscience, Inc. Longo is a founder of, board member of, and consultant for and has financial interest in PharmatrophiX, a company focused on small-molecule development for treatment of neurodegenerative disorders.

Please see the published study for a full listing of authors and funding sources.

END


ELSE PRESS RELEASES FROM THIS DATE:

Life after (feigned) death

Life after (feigned) death
2024-08-22
A new study led by scientists from the University of Bristol has revealed what animals do after they have feigned death in order to avoid being killed by a predator and what the context of this behaviour is. Many animals, as a last-ditch defence, become motionless after being contacted by a predator. This behaviour is so common that it's recognised in such phrases as “playing possum”. It is even said to occur in humans in extreme circumstances.  In previous studies, carried out by the same team using antlion larvae, scientists noticed that they become motionless after being individually handled. At one point ...

Fisheries research overestimates fish stocks

2024-08-22
Many fish stocks around the world are either threatened by overfishing or have already collapsed. One of the main reasons for this devastating trend is that policymakers have often ignored the catch limits calculated by scientists, which were intended to be strict thresholds to protect stocks. But it has now become clear that even these scientific recommendations were often too high. In the European Union (EU), for example, fisheries are primarily managed through allowable catch limits, known as quotas, which are set by the European ...

AI tackles one of the most difficult challenges in quantum chemistry

2024-08-22
New research using neural networks, a form of brain-inspired AI, proposes a solution to the tough challenge of modelling the states of molecules. The research shows how the technique can help solve fundamental equations in complex molecular systems. This could lead to practical uses in the future, helping researchers to prototype new materials and chemical syntheses using computer simulation before trying to make them in the lab. Led by Imperial College London and Google DeepMind scientists, the study is published today in Science. Excited molecules The team investigated the problem of understanding ...

Mitochondria are flinging their DNA into our brain cells

Mitochondria are flinging their DNA into our brain cells
2024-08-22
NEW YORK, NY (Aug. 22, 2024)--As direct descendants of ancient bacteria, mitochondria have always been a little alien. Now a study shows that mitochondria are possibly even stranger than we thought.  Mitochondria in our brain cells frequently fling their DNA into the nucleus, the study found, where the DNA becomes integrated into the cells’ chromosomes. And these insertions may be causing harm: Among the study’s nearly 1,200 participants, those with more mitochondrial DNA insertions in their brain cells ...

Revealing DNA behavior in record time

Revealing DNA behavior in record time
2024-08-22
“DNA, RNA and proteins are the key players to regulate all processes in the cells of our body,” Leiden Professor John van Noort explains. “To understand the (mis-)functioning of these molecules, it is essential to uncover how their 3D structure depends on their sequence and for this it is necessary to measure them one molecule at a time. However, single-molecule measurements are laborious and slow, and the number of possible sequence variations is massive.” From decades to days Now the team of scientists developed an innovative tool, called SPARXS (Single-molecule Parallel Analysis for Rapid eXploration ...

Columbia receives $400 million gift for biomedical research

Columbia receives $400 million gift for biomedical research
2024-08-22
NEW YORK, NY (Aug. 22, 2024)--Columbia University announced today a new $400 million gift from Roy and Diana Vagelos, which will secure Columbia’s leadership in biomedical science research and education and produce a vast array of compelling opportunities for improving society’s health and wellbeing. The gift is the single largest ever made to Columbia’s medical school and, taken together with their previous giving, establishes Roy and Diana as the most generous donors in the history of Columbia University.  A ...

Air pollution harms mental health worse in New York’s historically redlined neighborhoods

Air pollution harms mental health worse in New York’s historically redlined neighborhoods
2024-08-22
BUFFALO, N.Y. — Air pollution is bad for mental health. That much is clear. Now, new research shows the impact may be even worse in neighborhoods that were historically redlined.  University at Buffalo researchers looked at 17 cities across New York State where longstanding federal housing policies once denied neighborhoods with people of color from receiving mortgages. Although this practice was outlawed in 1968, the researchers found that elevated levels of air pollutants in these neighborhoods of the state ...

Meteor showers shed light on where comets formed in the early solar system

Meteor showers shed light on where comets formed in the early solar system
2024-08-22
An international team of 45 researchers studying meteor showers has found that not all comets crumble the same way when they approach the Sun. In a paper published in the journal Icarus this week, they ascribe the differences to the conditions in the protoplanetary disk where comets formed 4.5 billion years ago. “The meteoroids we see as meteors in the night sky are the size of small pebbles,” said lead author and SETI Institute and NASA Ames meteor astronomer Peter Jenniskens. “They are, in fact, the same size as the pebbles that collapsed into comets during the formation of ...

ChatGPT shows promise in answering patients' questions to urologists

2024-08-22
August 22, 2024 — The groundbreaking ChatGPT chatbot shows potential as a time-saving tool for responding to patient questions sent to the urologist's office, suggests a study in the September issue of Urology Practice®, an Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.  The artificial intelligence (AI) tool generated "acceptable" responses to nearly one-half of a sample of real-life patient questions, according to the new research ...

T cells manipulate the memory of innate immune cells

2024-08-22
Research from Radboud university medical center reveals that T cells from the adaptive immune system can manipulate the memory of innate immune cells. Previously, it was believed that the memory of innate immune cells operated independently. This surprising connection opens up new possibilities for the treatment of various diseases. A mouse model shows that no immunosuppressive drugs are needed after an organ transplantation if this  interaction between T cells and the innate immunity is temporarily blocked after the transplantation. The adaptive immune ...

LAST 30 PRESS RELEASES:

Less intensive works best for agricultural soil

Arctic rivers project receives “national champion” designation from frontiers foundation

Computational biology paves the way for new ALS tests

Study offers new hope for babies born with opioid withdrawal syndrome

UT, Volkswagen Group of America celebrate research partnership

New Medicare program could dramatically improve affordability for cancer drugs – if patients enroll

Are ‘zombie’ skin cells harmful or helpful? The answer may be in their shapes

University of Cincinnati Cancer Center presents research at AACR 2025

Head and neck, breast, lung and survivorship studies headline Dana-Farber research at AACR Annual Meeting 2025

AACR: Researchers share promising results from MD Anderson clinical trials

New research explains why our waistlines expand in middle age

Advancements in muon detection: Taishan Antineutrino Observatory's innovative top veto tracker

Chips off the old block

Microvascular decompression combined with nerve combing for atypical trigeminal neuralgia

Cutting the complexity from digital carpentry

Lung immune cell type “quietly” controls inflammation in COVID-19

Fiscal impact of expanded Medicare coverage for GLP-1 receptor agonists to treat obesity

State and sociodemographic trends in US cigarette smoking with future projections

Young adults drive historic decline in smoking

NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research

Chimpanzee stem cells offer new insights into early embryonic development

This injected protein-like polymer helps tissues heal after a heart attack

FlexTech inaugural issue launches, pioneering interdisciplinary innovation in flexible technology

In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity

Methyl eugenol: potential to inhibit oxidative stress, address related diseases, and its toxicological effects

A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions

AI helps unravel a cause of Alzheimer's disease and identify a therapeutic candidate

Coalition of Autism Scientists critiques US Department of Health and Human Services Autism Research Initiative

Structure dictates effectiveness, safety in nanomedicine

Mission accomplished for the “T2T” Hong Kong Bauhinia Genome Project

[Press-News.org] Drugs that improve brain metabolism could help Alzheimer’s patients