Researchers at the National Eye Institute (NEI) have determined how certain short protein fragments, called peptides, can protect neuronal cells found in the light-sensing retina layer at the back of the eye. The peptides might someday be used to treat degenerative retinal diseases, such as age-related macular degeneration (AMD). The study was published online on June 16, 2021 in the Journal of Neurochemistry. The article is titled “”Pigment Epithelium-Derived Factor (PEDF) and Derived Peptides Promote Survival and Differentiation of Photoreceptors and Induce Neurite-outgrowth in Amacrine Neurons.” The NEI is part of the National Institutes of Health (NIH). A team led by Patricia Becerra, PhD, Chief of the NEI Section on Protein Structure and Function, had previously derived these peptides from a protein called pigment epithelium-derived factor (PEDF) (image), which is produced by retinal pigment epithelial cells that line the back of the eye.
by Michael A. Goldman,* PhD, Professor & Former Chair, Biology, San Francisco State University (SFSU).
No engineer would build a bridge and gingerly drive over it today without first simulating the structure and its resilience using computer models. Why then should pharmaceutical companies test drugs in animals and people without sophisticated simulation first? Speaking at the virtual Precision Medicine World Conference (PMWC) 2021 (June 14-18) symposium on artificial intelligence and data science today (6/15/2021), Siddhartha Roychoudhury, PhD, Global Product General Manager at Amgen, says “Clinical trial design is still stuck in the 1970’s.”
Although each organism has a unique genome, a single sequence of genes, each individual has many epigenomes. An epigenome consists of chemical compounds and proteins that can bind to DNA and regulate gene action, either by activating or deactivating them or producing organ- or tissue-specific proteins. As it is a highly dynamic material, it can provide a large amount of information to shed light on the evolution of the various tissues and organs that make up the body. Now, a team from the Institute of Evolutionary Biology (IBE), a joint center of the Spanish National Research Council (CSIC) and Pompeu Fabra University (Barcelona), has carried out the largest study to date on the regulatory elements in the genome of primates.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease (named after famous American baseball player who died of the disease), is a neurodegenerative disease that strikes nearly 5,000 people in the U.S. every year. About 10% of ALS cases are inherited or familial, often caused by an error in the C9orf72 gene. Compared to sporadic or non-familial ALS, C90rf72 patients are considered to have a more aggressive disease course. Evidence points to the immune system in disease progression in C90rf72 patients, but we know little of what players are involved. New research from the Jefferson Weinberg ALS Center of Jefferson Health in Philadelphia identified an increased inflammatory signal in C90rf72 patients compared to other ALS patients, pointing to immune characteristics that distinguish this subgroup of ALS patients and informing potential anti-inflammatory therapies. The study was published online in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration on April 30th, 2021. The article is titled “Increased Synthesis of Pro-Inflammatory Cytokines in C9ORF72 Patients.”
Cells contain machinery that duplicates DNA into a new set that goes into a newly formed cell. That same class of machines, called polymerases, also build RNA messages, which are like notes copied from the central DNA repository of recipes, so they can be read more efficiently into proteins. But polymerases were thought to only work in one direction DNA into DNA or RNA. This prevents RNA messages from being rewritten back into the master recipe book of genomic DNA. Now, Thomas Jefferson University researchers provide the first evidence that RNA segments can be written back into DNA, which potentially challenges the central dogma in biology and could have wide implications affecting many fields of biology. “This work opens the door to many other studies that will help us understand the significance of having a mechanism for converting RNA messages into DNA in our own cells,” says Richard Pomerantz, PhD, Associate Professor of Biochemistry and Molecular Biology at Thomas Jefferson University in Philadelphia. “The reality that a human polymerase can do this with high efficiency, raises many questions.” For example, this finding suggests that RNA messages can be used as templates for repairing or re-writing genomic DNA. The work was published online on June 11, 2021 in the journal Science Advances. The open-access article is titled “Polθ Reverse Transcribes RNA and Promotes RNA-Templated DNA Repair.”
On March 30, 2021, Oncotarget published “The Presence of Polymorphisms in Genes Controlling Neurotransmitter Metabolism and Disease Prognosis in Patients with Prostate Cancer: A Possible Link with Schizophrenia,” an open-access article reporting that polymorphisms of neurotransmitter metabolism genes had been studied in patients with prostate cancer (PC) characterized by either reduced or extended serum prostate-specific antigen (PSA) doubling time corresponding to unfavorable and favorable disease prognosis respectively. The following gene polymorphisms known to be associated with neuropsychiatric disorders were investigated: the STin2 VNTR in the serotonin transporter SLC6A4 gene; the 30-bp VNTR in the monoamine oxidase A MAOA gene; the Val158Met polymorphism in the catechol-ortho-methyltransferase COMT gene; and the promoter region C-521T polymorphism and the 48 VNTR in the third exon of the dopamine receptor DRD4 gene.
A study published in the June 10, 2021 issue of Cell describes a remarkable new mechanism by which the body’s own immune system can eliminate cancer cells without damaging host cells. The findings have the potential to develop first-in-class medicines that are designed to be selective for cancer cells and non-toxic to normal cells and tissues. If successful, this discovery may improve the practice of precision medicine by ensuring the right drug is delivered at the right dose at the right time. The article is titled “”Neutrophil Elastase Selectively Kills Cancer Cells and Attenuates Tumorigenesis.” (Image is of neutrophil).
The largest study of its kind has unveiled new insights into how genes are regulated in dementia, including the discovery of 84 genes newly associated with the disease. Led by scientists at the University of Exeter, the international collaboration combined and analyzed data from more than 1,400 people across six different studies, in a meta-analysis published online on June 10, 2021 in Nature Communications. The open-access article is titled “A Meta-Analysis of Epigenome-Wide Association Studies in Alzheimer’s Disease Highlights Novel Differentially Methylated Loci Across Cortex.”
A cell-penetrating peptide developed by researchers at Vanderbilt University Medical Center (VUMC) can prevent, in an animal model, the often-fatal septic shock that can result from bacterial and viral infections. The team’s findings, published online on June 7, 2021 in Scientific Reports, could lead to a way to protect patients at highest risk for severe complications and death from out-of-control inflammatory responses to microbial infections, including COVID-19. The open-access article is titled “Hyperlipidemic Hypersensitivity to Lethal Microbial Inflammation and Its Reversal by Selective Targeting of Nuclear Transport Shuttles.” “Life-threatening microbial inflammation hits harder (in) patients with metabolic syndrome, a condition afflicting millions of people in the United States and worldwide,” said the paper’s corresponding author, Jacek Hawiger, MD, PhD, the Louise B. McGavock Chair in Medicine and Distinguished Professor of Medicine at VUMC. An international authority on inflammation as the mechanism of multiple diseases, Dr. Hawiger also is Professor of Molecular Physiology and Biophysics at Vanderbilt and a Health Research Scientist at the Nashville Veterans Affairs (VA) Medical Center.
People with Parkinson’s disease (PD) may spend years struggling with debilitating symptoms, including loss of balance and coordination, inability to move, and difficulty speaking and swallowing. Available treatments only address the symptoms of the disease, not the underlying cause–and because patients can live with the disease for a long time, the effectiveness of current treatments wanes over time. New treatments are needed that can help stave off debilitating symptoms and help patients retain their independence longer. Now, researchers in the Drug Discovery Lab at UCLA Health have identified a new class of drugs for Parkinson’s based on studies using human cells and in mice. The compound works by reducing the transmission of damaging proteins from affected brain cells to their neighbors. The findings, published online on April 19, 2021 in Molecular Brain, introduce a possible new approach to treating Parkinson’s disease. The open-access article is titled “Pharmacological Inhibition of nSMase2 Reduces Brain Exosome Release and α-Synuclein Pathology in a Parkinson’s Disease Model.”