Strategies For Complicated Neurodegenerative Disorders — Dr. Leonard Petrucelli, PhD — Neurodegenerative Diseases Laboratory, Department of Neuroscience, Mayo Clinic.
Category: biotech/medical – Page 6

Scientists are collecting toenail clippings to reveal radon exposure and lung cancer risk
At 47 years of age, Emi Bossio was feeling good about where she was. She had a successful law practice, two growing children and good health. Then she developed a nagging cough. The diagnosis to come would take her breath away.
“I never smoked, never. I ate nutritiously and stayed fit. I thought to myself, I can’t have lung cancer,” says Bossio. “It was super shocking. A cataclysmic moment. There are no words to describe it.”
Bossio had to give up her law practice to focus on treatment and healing. As part of that journey, she’s taken on a new role as an advocate to increase awareness about lung cancer. She still has no idea what caused her lung cancer. Trying to answer that question is how Bossio became interested in the research Dr. Aaron Goodarzi, Ph.D., is doing at the University of Calgary.


Synaptic Dysfunction in Dementia Can Be Modelled in Patient-Derived Neurons
Neurons produced from frontotemporal dementia patients’ skin biopsies using modern stem cell technology recapitulate the synaptic loss and dysfunction detected in the patients’ brains, a new study from the University of Eastern Finland shows.
Frontotemporal dementia is a progressive neurodegenerative disease affecting the frontal and temporal lobes of the brain. The most common symptoms are behavioral changes, difficulties in understanding or producing speech, problems in movement, and psychiatric symptoms. Often, frontotemporal dementia has no identified genetic cause, but especially in Finnish patients, hexanucleotide repeat expansion in the C9orf72 gene is a common genetic cause, present in about half of the familial cases and in 20 per cent of the sporadic cases where there is no family history of the disease. However, the disease mechanisms of the different forms of frontotemporal dementia are still poorly understood, and there are currently no effective diagnostic tests or treatments affecting the progression of the disease in clinical use.
Brain imaging and neurophysiological studies have shown that pathological and functional changes underlying the symptoms occur at synapses, the connections between brain neurons, in frontotemporal dementia patients. PET imaging studies have shown significant synapse loss in the brain, and transcranial magnetic stimulation, on the other hand, has indicated disturbed function of both excitatory and inhibitory neurotransmitter systems, leading to deficient neurotransmission. Often, drugs affecting the different neurotransmitter systems are used to mitigate the symptoms of frontotemporal dementia patients.

Chinese medicine extract tetrandrine’s precise mechanism of action opens new avenues for drug discovery
With this discovery, the researchers propose that tetrandrine can be used to disrupt processes critical to the survival and replication of viruses, such as Ebola and COVID-19, by targeting LIMP-2 to alter lysosomal calcium release.
Importantly, these findings highlight lysosome-related mechanisms as a new frontier for drug discovery, offering novel strategies for treating diseases caused by calcium imbalance, including neurodegenerative disorders like Alzheimer’s and Parkinson’s, as well as certain metastatic cancers.
Prof. Ko said, “This is the first time a function of LIMP-2 in calcium signaling has been uncovered. From a cell biology perspective, our study has revealed a completely new pathway for NAADP-regulated calcium signaling, through LIMP-2 and sphingosine. From an anti-viral treatment perspective, the study has identified LIMP-2 as a key target of tetrandrine for the treatment of Ebola virus infection, with broader applications in other antiviral therapies.”


MIT and Harvard Build “Invisible” Immune Cells That Obliterate Cancer
MIT and Harvard scientists have created engineered CAR-NK cells that can hide from the immune system and more effectively destroy cancer.
The cells are designed to suppress immune-rejection signals and enhance tumor-killing power. Tested in humanized mice, they wiped out cancer while avoiding dangerous immune reactions.
A major breakthrough in immune engineering.

It’s all in your head: Select neurons in the brainstem may hold the key to treating chronic pain
Acute or short-lived pain, despite its bad reputation, is usually a lifesaver. It acts as a transient negative sensory experience that helps us avoid danger. Touch a hot stove, stub a toe, or bonk your head on a low branch, and the nervous system cues up an “Ow!” Over time, the sting fades, the wound heals, but the lesson sticks.
Chronic pain is different; the alarm keeps blaring long after the fire is out, and then the pain itself becomes the problem. Nearly 50 million people in the United States live with chronic pain, an invisible and often untreatable condition that can linger for decades. “It’s not just an injury that won’t heal,” says neuroscientist at the University of Pennsylvania J. Nicholas Betley, “it’s a brain input that’s become sensitized and hyperactive, and determining how to quiet that input could lead to better treatments.”
Now, research led by Betley and collaborators at the University of Pittsburgh and Scripps Research Institute has identified a key to regulating long-term pain states: a group of cells called Y1 receptor (Y1R)-expressing neurons in the brainstem’s lateral parabrachial nucleus (lPBN). These neurons are activated during enduring pain states, but they also integrate information about hunger, fear and thirst, allowing for pain signals to be modulated by other brain circuits signaling more urgent needs.


1,000-year-old gut microbiome revealed for young man who lived in pre-Hispanic Mexico
Analysis of preserved feces and intestinal tissue has revealed specific types of bacteria that were present in the microbiome of a young adult man who lived in Mexico about 1,000 years ago, prior to Spanish colonization. Santiago Rosas-Plaza of Universidad Nacional Autónoma de México and colleagues present these findings in PLOS One.
The human gut microbiome consists of microorganisms, including bacteria, that naturally live in people’s intestines. Certain types of bacteria are widely associated with the human gut microbiome, but a person’s particular mix of bacteria may vary depending on factors such as age, diet, health, and where they live. Studying ancient microbiomes using mummies and human remains can therefore deepen understanding of ancient populations and show how the human microbiome may have changed over time.
A growing number of ancient microbiomes have been revealed, including for an ancient Incan person and Germany’s “Tyrolean Iceman.” To further expand the field, Rosas-Plaza and colleagues analyzed the exceptionally well-preserved remains of a man discovered in a rock shelter in Zimapán, Mexico. Prior analyses suggest the “Zimapán man” was most likely a seasonal seminomadic hunter-gatherer who was part of the ancient Mesoamerican Otopame culture and died about 1,000 years ago between the ages of 21 and 35.