540 results match your criteria: "Huffington Center on Aging.[Affiliation]"
Nat Commun
August 2020
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Current efforts in the proteolysis targeting chimera (PROTAC) field mostly focus on choosing an appropriate E3 ligase for the target protein, improving the binding affinities towards the target protein and the E3 ligase, and optimizing the PROTAC linker. However, due to the large molecular weights of PROTACs, their cellular uptake remains an issue. Through comparing how different warhead chemistry, reversible noncovalent (RNC), reversible covalent (RC), and irreversible covalent (IRC) binders, affects the degradation of Bruton's Tyrosine Kinase (BTK), we serendipitously discover that cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular accumulation and target engagement of PROTACs and develop RC-1 as a reversible covalent BTK PROTAC with a high target occupancy as its corresponding kinase inhibitor and effectiveness as a dual functional inhibitor and degrader, a different mechanism-of-action for PROTACs.
View Article and Find Full Text PDFSci Rep
August 2020
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Transcription is regulated through a dynamic interplay of DNA-associated proteins, and the composition of gene-regulatory complexes is subject to continuous adjustments. Protein alterations include post-translational modifications and elimination of individual polypeptides. Spatially and temporally controlled protein removal is, therefore, essential for gene regulation and accounts for the short half-life of many transcription factors.
View Article and Find Full Text PDFInt J Mol Med
September 2020
School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
Bioactive peptides are an emerging area of biomedical research in the study of numerous human diseases, including acute alcoholic liver injury (AALI). To study the role and mechanism of the milk‑derived hexapeptide Pro‑Gly‑Pro‑Ile‑Pro‑Asn (PGPIPN) in preventing and reducing AALI, the present study established a mouse model of AALI. PGPIPN was used as a therapeutic drug, and glutathione (GSH) was used as a positive control.
View Article and Find Full Text PDFCell Rep
July 2020
Sage Bionetworks, Seattle, WA 98121, USA. Electronic address:
We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders.
View Article and Find Full Text PDFTrends Biochem Sci
November 2020
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Lysosomes transcend the role of degradation stations, acting as key nodes for interorganelle crosstalk and signal transduction. Lysosomes communicate with the nucleus through physical proximity and functional interaction. In response to external and internal stimuli, lysosomes actively adjust their distribution between peripheral and perinuclear regions and modulate lysosome-nucleus signaling pathways; in turn, the nucleus fine-tunes lysosomal biogenesis and functions through transcriptional controls.
View Article and Find Full Text PDFProtein Cell
July 2020
Huffington Center on Aging, Baylor College of Medicine, Houston, TX, 77030, USA.
Alzheimers Dement
July 2020
Medical & Scientific Relations, Alzheimer's Association, Chicago, Illinois, USA.
From its inception in 1980, advancement of research was one of the primary missions of the Alzheimer's Association (also known as Alzheimer's Disease and Related Disorders Association) in addition to leading in family caregiver support, better care, public education, and awareness. Over the past 30 years, the Association has grown and expanded its engagement with the scientific community. In the past 10 years, its research budget has more than doubled, greatly increasing the number of research grants funded and the number of strategic projects supported.
View Article and Find Full Text PDFMethods Mol Biol
March 2021
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
The replicative aging of the budding yeast, Saccharomyces cerevisiae, has been a useful model for dissecting the molecular mechanisms of the aging process. Traditionally, the replicative lifespan (RLS) is measured by manually dissecting mother cells from daughter cells, which is a very tedious process. Since 2012, several microfluidic systems have been developed to automate the dissection process, significantly accelerating RLS determination.
View Article and Find Full Text PDFElife
May 2020
Department of Neuroscience, Baylor College of Medicine, Houston, United States.
Structural changes in pre and postsynaptic neurons that accompany synapse formation often temporally and spatially overlap. Thus, it has been difficult to resolve which processes drive patterned connectivity. To overcome this, we use the laminated outer murine retina.
View Article and Find Full Text PDFMol Psychiatry
October 2021
Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.
Neurofibrillary tangles (NFTs) composed of hyperphosphorylated and misfolded tau protein are a pathological hallmark of Alzheimer's disease and other tauopathy conditions. Tau is predominantly an intraneuronal protein but is also secreted in physiological and pathological conditions. The extracellular tau has been implicated in the seeding and propagation of tau pathology and is the prime target of the current tau immunotherapy.
View Article and Find Full Text PDFNat Commun
March 2020
Huffington Center on Aging, Baylor College of Medicine, Houston, TX, 77030, USA.
Olfactory and metabolic dysfunctions are intertwined phenomena associated with obesity and neurodegenerative diseases; yet how mechanistically olfaction regulates metabolic homeostasis remains unclear. Specificity of olfactory perception integrates diverse environmental odors and olfactory neurons expressing different receptors. Here, we report that specific but not all olfactory neurons actively regulate fat metabolism without affecting eating behaviors in Caenorhabditis elegans, and identified specific odors that reduce fat mobilization via inhibiting these neurons.
View Article and Find Full Text PDFAging Cell
April 2020
State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China.
Histone acetyltransferases (HATs) are important enzymes that transfer acetyl groups onto histones and thereby regulate both gene expression and chromosomal structures. Previous work has shown that the activation of sirtuins, which are histone deacetylases, can extend lifespan. This suggests that inhibiting HATs may have a similar beneficial effect.
View Article and Find Full Text PDFElife
February 2020
Department of Neurobiology and Anatomy, The University of Texas McGovern Medical School at Houston, Houston, United States.
Type I interferon (IFN) is a key cytokine that curbs viral infection and cell malignancy. Previously, we demonstrated a potent IFN immunogenicity of nucleic acid-containing (NA-containing) amyloid fibrils in the periphery. Here, we investigated whether IFN is associated with β-amyloidosis inside the brain and contributes to neuropathology.
View Article and Find Full Text PDFHum Genet
March 2020
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, USA.
Dysfunction and dysregulation at multiple levels, from organismal to molecular, are associated with the biological process of aging. In a eukaryotic nucleus, multiple lines of evidence have shown that the fundamental structure of chromatin is affected by aging. Not only euchromatic and heterochromatic regions shift locations, global changes, such as reduced levels of histones, have been reported for certain aged cell types and tissues.
View Article and Find Full Text PDFNeural Dev
December 2019
Department of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, TX, 77030, USA.
Microglia are increasingly shown to be key players in neuron development and synapse connectivity. However, the underlying mechanisms by which microglia regulate neuron function remain poorly understood in part because such analysis is challenging in the brain where neurons and synapses are intermingled and connectivity is only beginning to be mapped. Here, we discuss the features and function of microglia in the ordered mammalian retina where the laminar organization of neurons and synapses facilitates such molecular studies.
View Article and Find Full Text PDFCell Signal
February 2020
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address:
Mitochondria plays a key role in regulating cell death process under stress conditions and it has been indicated that NAMPT overexpression promotes cell survival under genotoxic stress by maintaining mitochondrial NAD level. NAMPT is a rate-limiting enzyme for NAD production in mammalian cells and it was suggested that NAMPT and NMNAT3 are responsible for mitochondrial NAD production to maintain mitochondrial NAD pool. However, subsequent studies suggested mitochondrial may lack the NAMPT-NMANT3 pathway to maintain NAD level.
View Article and Find Full Text PDFG3 (Bethesda)
January 2020
Molecular and Human Genetics,
Trends Cell Biol
November 2019
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Lysosomes are sites of active metabolism in a cell. They contain various hydrolases that degrade extracellular and intracellular materials during endocytosis and autophagy, respectively. In addition to their long-recognized roles in degradation and recycling, emerging studies have revealed that lysosomes are organizing centers for signal transduction.
View Article and Find Full Text PDFJ Comp Neurol
April 2020
Department of Neuroscience, Baylor College of Medicine, Houston, Texas.
In several areas of the central nervous system, neurons are regionally organized into groups or layers that carry out specific activities. In this form of patterning, neurons of distinct types localize their cell bodies to just one or a few of the layers within a structure. However, little is known about whether diverse neuron types within a lamina share molecular features that coordinate their organization.
View Article and Find Full Text PDFHum Mol Genet
March 2020
Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, USA.
Neuron
September 2019
Huffington Center on Aging and Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Starting your own academic lab is a wonderful opportunity to impact science through research and trainee mentoring. In this article, we share some thoughts and resources for this undertaking in the hope that they may enhance the experience of others.
View Article and Find Full Text PDFMol Cell Oncol
July 2019
Department of Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
Telomeres and sirtuins are independently implicated in causing disease and aging, but how they cooperate is not well understood. A recent study demonstrates that telomere shortening represses sirtuins and increasing sirtuin activity stabilizes telomeres and improves telomere-dependent disease, suggesting that these two pathways are tightly intertwined.
View Article and Find Full Text PDFStem Cell Reports
October 2019
A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70211, Finland. Electronic address:
Here we elucidate the effect of Alzheimer disease (AD)-predisposing genetic backgrounds, APOE4, PSEN1ΔE9, and APPswe, on functionality of human microglia-like cells (iMGLs). We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny from yolk sac.
View Article and Find Full Text PDFSci Adv
July 2019
Department of Molecular and Human Genetics, and Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
Changes in chromatin organization occur during aging. Overexpression of histones partially alleviates these changes and promotes longevity. We report that deletion of the histone H3-H4 minor locus extended the replicative life span of .
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