Weizmann Institute scientists have discovered two small molecules that can cross the blood-brain barrier in mice, slowing and even reversing the effects of Huntington's, which is incurable.
The human brain is a well-guarded control center. Its system of blood vessels is surrounded by a densely packed cellular barrier that prevents most substances from getting in or out. This fortified architecture protects the brain, but it can also stop it from getting help when it needs it—for example, in the case of a neurodegenerative disease.
In a new study, published in EMBO Molecular Medicine, Prof. Rivka Dikstein of the Weizmann Institute of Science and her team identified two small molecules that manage to penetrate the blood-brain barrier and reduce the levels of a defective protein that causes Huntington's disease, an incurable neurodegenerative disorder. The new drugs not only slowed the progress of the disease in mouse models but even reversed some of its symptoms.
The signs and symptoms of Huntington's disease—slight involuntary movements, general clumsiness and increased anxiety—most commonly emerge around the age of 40. The disease develops over time and inevitably leads to death. It is caused by an excessive repetition, 36 times or more, of a DNA segment in the huntingtin gene.
Navigating Cognitive Decline: Curved Walking and Depth Cameras Unveil Early Signs
MARCH 12, 2024
First-of-its-kind study finds more gait impairments in older adults by ‘throwing them a curve’.
A first-of-its-kind study suggests that to detect subtle gait impairments in older adults that often are prevalent in the early stages of cognitive decline, “throw them a curve.”
Gait analysis, examining the way an individual stands and walks, is emerging as a valuable, non-invasive complement to cognitive assessments that aid in early diagnosis and management. In clinical settings, gait and balance tests typically focus on a straight walking path.
Exploring Curved Path Walking
This new study ventures into a different realm – curved path walking – a more natural yet complex activity. Straight walking is a rhythmic and simpler activity, whereas walking on a curving path requires greater cognitive and motor skills such as a transition time to change directions and correct balance.
College of Engineering and Computer Science researchers at Florida Atlantic University are the first to quantitatively compare the performance of healthy older adults versus older adults with mild cognitive impairment (MCI) in straight and curve walking. MCI is the early stage of cognitive decline and people with MCI have a much higher risk of transitioning to Alzheimer’s disease (AD).
Microbes stomp daffodils in creating valuable anti-Alzheimer's drug
By Michael Franco
March 15, 2024
https://newatlas.com/medical/microbes-a ... mers-drug/
Using an AI-based approach, researchers found a better way to create the drug galantamine, commonly prescribed to people suffering from Alzheimer's and other forms of dementia. The fermentation-based technique could boost the drug's availability.
While bacteria are perhaps most famous for causing diseases like strep throat and pneumonia, the tiny microbes can also be programmed to serve as the workhorses in chemical processes. For example, we've seen the probiotic Lactobacillus reuteri genetically engineered to secrete a rheumatoid arthritis drug in the body, and a modified strain of E.coli Nissle 1917 used to produce the anti-Parkinson's Disease drug L-DOPA.
Now, a team of researchers from the University of Texas (UT) has called upon E. Coli once again, this time to produce the anti-dementia drug galantamine. Galantamine works by slowing the breakdown of acetylcholine in the brain, which is an important neurotransmitter that is often degraded in the face of Alzheimer's disease and other cases of dementia. The active ingredient in galantamine is typically extracted from daffodils but that production method is time consuming and subject to the challenges faced by growing and harvesting any crop.
A team of neurologists, stem cell specialists and molecular biologists affiliated with several institutions in the U.S. and led by a group at Stanford University School of Medicine has found evidence that the root cause of Alzheimer's disease may be fat buildup in brain cells. The study is published in the journal Nature.
Prior research has suggested that Alzheimer's disease is caused by a buildup of beta-amyloid in plaques that grow between nerve cells. Other work has also implicated a protein called tau, which can build up in brain cells. Thus, most work involved in developing ways to prevent, slow or stop the disease is based on reducing or eliminating such buildups. But as the researchers with this new effort have found, there may be something else at the root of the development of the disease.
Back when Alzheimer's disease was first identified by Alois Alzheimer, he noted that in addition to the plaques and tau buildup, there was also a buildup of fat droplets in brain cells. Since that time, little effort has been made to determine whether they might be the cause of the disease.
In a paper published in the Journal of the American Medical Association (JAMA), neurologists at Beth Israel Deaconess Medical Center (BIDMC) showed that a simple skin biopsy test detects an abnormal form of alpha-synuclein, the pathological hallmark of Parkinson's disease and the subgroup of neurodegenerative disorders known as synucleinopathies, at high positivity rates.
Results from this landmark study validate this cutaneous method as a reliable and convenient tool to help physicians make more accurate diagnoses for patients and support future clinical trials for investigational drugs targeting alpha-synuclein.
A team of neurologists, stem cell specialists and molecular biologists affiliated with several institutions in the U.S. and led by a group at Stanford University School of Medicine has found evidence that the root cause of Alzheimer's disease may be fat buildup in brain cells. The study is published in the journal Nature.
Prior research has suggested that Alzheimer's disease is caused by a buildup of beta-amyloid in plaques that grow between nerve cells. Other work has also implicated a protein called tau, which can build up in brain cells. Thus, most work involved in developing ways to prevent, slow or stop the disease is based on reducing or eliminating such buildups. But as the researchers with this new effort have found, there may be something else at the root of the development of the disease.
Back when Alzheimer's disease was first identified by Alois Alzheimer, he noted that in addition to the plaques and tau buildup, there was also a buildup of fat droplets in brain cells. Since that time, little effort has been made to determine whether they might be the cause of the disease.
I'm just wondering why no one investigated this earlier?
The survival of neurons, unlike most other cells in the body, depends largely on the energy provided by mitochondria, intracellular organelles that contain their DNA to function properly.
The presence of mitochondrial DNA with deletions—the loss of fragments of DNA sequence—in cerebrospinal fluid could be an early marker of severe brain disease and an initial link in the whole neurodegenerative process, leading to the motor and cognitive symptoms associated with these disorders.
This is one of the main conclusions of the article published in the journal eBioMedicine.
The team was led by Álex Iranzo, professor at the Faculty of Medicine and Health Sciences of the University of Barcelona and director of the UB-AdSalutem Chair on Sleep and its Disorders, head of the Neurology Service of the Hospital Clinic of Barcelona, and of the clinical neurophysiology research group of the August Pi i Sunyer Biomedical Research Institute (IDIBAPS), and Ramon Trullàs, researcher of the Spanish National Research Council at the Barcelona Biomedical Research Institute (IIBB-CSIC); both linked to the Center for Biomedical Research Network in Neurodegenerative Diseases (CIBERNED).
Beyond plaques: New Alzheimer's treatment pathway discovered
By Michael Franco
March 27, 2024
https://newatlas.com/medical/pde4b-alzh ... t-pathway/
Researchers have discovered that limiting a certain enzyme can have a dramatic impact in protecting against the effects of Alzheimer's disease. The finding could lead to a new class of drugs that fight the disease.
Much of the historical research into Alzheimer's disease has focused on plaques that form in the brain thanks to the accumulation of too much amyloid proteins. Recently, though, scientists have begun looking beyond the role of these proteins (which one study suggests may form in the liver) into other probable causes of the disease and its advancement. That's largely because amyloid-based plaques, while certainly a hallmark of the disease, don't seem to be a direct cause of it, as evidenced by the failure of drugs that try to target them.
In seeking another way forward, researchers at the University of Leeds (UL) and Lancaster University (LU) in the UK, turned to an Australian study that showed that having the gene for the production of an enzyme known as PDE4B was identified as a risk factor for developing Alzheimer's.
