New Brain Death Pathway In Alzheimer’s Identified

Findings of team led by the Arizona State University (ASU) scientists offer hope for therapies targeting cell loss in the brain, an inevitable and devastating outcome of Alzheimer’s progression
Alzheimer’s disease tragically ravages the brains, memories and, ultimately, personalities of its victims. Now affecting 5 million Americans, Alzheimer’s disease is the sixth-leading cause of death in the U.S., and a cure for Alzheimer’s remains elusive, as the exact biological events that trigger it are still unknown.

In a new study, Arizona State University-Banner Health neuroscientist Salvatore Oddo and his colleagues from Phoenix’s Translational Genomics Research Institute (TGen) — as well as the University of California, Irvine, and Mount Sinai in New York — have identified a new way for brain cells to become fated to die during Alzheimer’s disease. The research team has found the first evidence that the activation of a biological pathway called necroptosis, which causes neuronal loss, is closely linked with Alzheimer’s severity, cognitive decline and extreme loss of tissue and brain weight that are all advanced hallmarks of the disease.

We anticipate that our findings will spur a new area of Alzheimer’s disease research focused on further detailing the role of necroptosis and developing new therapeutic strategies aimed at blocking it,” said Oddo, the lead author of this study, and scientist at the ASU-Banner Neurodegenerative Disease Research Center at the Biodesign Institute and associate professor in the School of Life Sciences.

Necroptosis, which causes cells to burst from the inside out and die, is triggered by a triad of proteins. It has been shown to play a central role in multiple sclerosis and Lou Gehrig’s disease (amyotrophic lateral sclerosis, or ALS), and now for the first time, also in Alzheimer’s disease.

There is no doubt that the brains of people with Alzheimer’s disease have fewer neurons,” explained Oddo. “The brain is much smaller and weighs less; it shrinks because neurons are dying. That has been known for 100 years, but until now, the mechanism wasn’t understood.
The findings appear in the advanced online edition of Nature Neuroscience.

Source: https://asunow.asu.edu/

Tatoo Therapy

A temporary tattoo to help control a chronic disease might someday be possible, according to scientists at Baylor College of Medicine who tested antioxidant nanoparticles created at Rice University. A proof-of-principle study led by Baylor scientist Christine Beeton published by Nature’s online, open-access journal Scientific Reports shows that nanoparticles modified with polyethylene glycol are conveniently choosy as they are taken up by cells in the immune system. That could be a plus for patients with autoimmune diseases like multiple sclerosis, one focus of study at the Beeton lab.

tatoo-therapy

“Placed just under the skin, the carbon-based particles form a dark spot that fades over about one week as they are slowly released into the circulation,” Beeton said. T and B lymphocyte cells and macrophages are key components of the immune system. However, in many autoimmune diseases such as multiple sclerosis, T cells are the key players. One suspected cause is that T cells lose their ability to distinguish between invaders and healthy tissue and attack both.

In tests at Baylor, nanoparticles were internalized by T cells, which inhibited their function, but ignored by macrophages. “The ability to selectively inhibit one type of cell over others in the same environment may help doctors gain more control over autoimmune diseases,” Beeton said. “The majority of current treatments are general, broad-spectrum immunosuppressants,” said Redwan Huq, lead author of the study and a graduate student in the Beeton lab. “They’re going to affect all of these cells, but patients are exposed to side effects (ranging) from infections to increased chances of developing cancer. So we get excited when we see something new that could potentially enable selectivity.” Since the macrophages and other splenic immune cells are unaffected, most of a patient’s existing immune system remains intact, he added.

 

Source: http://news.rice.edu/

Brain Cells Death Provokes Multiple Sclerosis

Multiple sclerosis* (MS) may be triggered by the death of brain cells that make myelin, the insulation around nerve fibers, according to research on a novel mouse model developed by scientists from the University of Chicago and Northwestern Medicine. The death of these cells initiates an autoimmune response against myelin, the main characteristic of the disease, which leads to MS-like symptoms in mice.This reaction can be prevented, however, through the application of specially developed nanoparticles, even after the loss of those brain cells. The nanoparticles are being developed for clinical trials that could lead to new treatments in humans.

multiple sclerosisAn image of the cerebellum from an animal early in the demyelinating phase of the late-onset disease. The green marks myelinated axons and the dark area in the center is a demyelinated lesion with T-cell inflammation (pink)

Although this was a study in mice, we’ve shown for the first time one possible mechanism that can trigger MS—the death of the cells responsible for generating myelin can lead to the activation of an autoimmune response against myelin,” said study co-senior author Brian Popko, the Jack Miller Professor of Neurological Disorders. “Protecting these cells in susceptible individuals might help delay or prevent MS.”

 

The study was published in Nature Neuroscience.

* Multiple sclerosis is a neurological disease involving an abnormal immune response against myelin, which leads to the progressive deterioration of a wide range of body functions. MS is thought to affect 2.5 million people worldwide, and has unclear causes and no known cure.

Source: http://news.uchicago.edu/