Results 71 to 80 of about 158,532 (263)

Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast

open access: yeseLife, 2020
Septin proteins evolved from ancestral GTPases and co-assemble into hetero-oligomers and cytoskeletal filaments. In Saccharomyces cerevisiae, five septins comprise two species of hetero-octamers, Cdc11/Shs1–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Cdc11/Shs1 ...
Courtney R Johnson   +6 more
doaj   +1 more source

Chronobiology of Cancer: How Aging Fuels Oncogenesis at the Molecular Level

open access: yesAging and Cancer, EarlyView.
This graphical abstract illustrates the key biological pathways linking aging with cancer development and progression. In the upper left, cumulative exposure to ultraviolet radiation, toxins, and reactive oxygen species (ROS) causes DNA damage and genomic instability, whereas age‐related decline in repair mechanisms, such as ATM/ATR, BER, and NER ...
Anu Singh, Aroonima Misra, Sufian Zaheer
wiley   +1 more source

The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling in C. elegans and in human cells

open access: yeseLife, 2020
The intracellular trafficking of growth factor receptors determines the activity of their downstream signaling pathways. Here, we show that the putative HSP-90 co-chaperone CHP-1 acts as a regulator of EGFR trafficking in C. elegans. Loss of chp-1 causes
Andrea Haag   +3 more
doaj   +1 more source

Unraveling 4‐Phenylbutyrate's Therapeutic Role in SLC6A1 Disorders: Pharmacochaperoning Over HDAC Inhibition

open access: yesAnnals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Objective Variants in SLC6A1, encoding the GABA transporter 1 (GAT‐1), cause epilepsy, autism spectrum disorder, and developmental delay via loss of GABA uptake, impaired trafficking, and ER retention. We previously found that 4‐Phenylbutyrate (PBA), an FDA‐approved drug, restores GABA uptake and reduces seizures in SLC6A1‐related disorders ...
Melissa B. DeLeeuw   +5 more
wiley   +1 more source

Re‐Purposing Sapropterin (Kuvan) for ACTA2‐Related Multisystemic Smooth Muscle Dysfunction Syndrome: A Translational Mechanistic and First‐In‐Human Therapeutic Report

open access: yesAnnals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Multisystemic smooth muscle dysfunction syndrome (MSMDS) is an ultra‐rare, ACTA2‐related disorder characterized by severe cerebrovascular disease, aortic aneurysms, and smooth muscle dysfunction. Using molecular dynamics simulations and in silico drug screening, we identified that sapropterin dihydrochloride (Kuvan) is a candidate capable of ...
Moran Hausman‐Kedem   +9 more
wiley   +1 more source

Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial Hsp90 TRAP1

open access: yeseLife, 2017
Hsp90 is a homodimeric ATP-dependent molecular chaperone that remodels its substrate ‘client’ proteins, facilitating their folding and activating them for biological function.
Daniel Elnatan   +5 more
doaj   +1 more source

Copper‐Driven Epithelial Barrier Disruption: A Novel Mechanism of COPD Acute Exacerbations Mediated by the TNF‐α/ATP7A Axis

open access: yesAdvanced Science, EarlyView.
This study reveals a copper‐driven mechanism of COPD acute exacerbations mediated by the TNF‐α/ATP7A axis. TNF‐α suppresses the copper transporter ATP7A via competitive NF‐κB/CREB1/CBP signaling, resulting in intracellular copper accumulation, mitochondrial oxidative stress, and epithelial barrier disruption.
Xinru Xiao   +7 more
wiley   +1 more source

Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control

open access: yeseLife, 2017
Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation.
Marta Carroni   +10 more
doaj   +1 more source

Gm26550 Modulates Learning and Memory by Increasing IGF1 mRNA Expression and Stability in Nrf2−/− Mice

open access: yesAdvanced Science, EarlyView.
The present study shows that Nrf2 directly binds to the Gm26550 promoter, thereby activating Gm26550 transcription and increasing its expression. Mechanistically, Gm26550 promotes IGF1 expression by functionally antagonizing miR‐26a‐5p‐mediated repression and sequestering the RBP KHSRP, thereby enhancing hippocampal neuronal synaptic plasticity and ...
Hongfang Wang   +12 more
wiley   +1 more source

Decreased Protein Quality Control Promotes the Cognitive Dysfunction Associated With Aging and Environmental Insults

open access: yesFrontiers in Neuroscience, 2018
Background: Most neurodegenerative diseases are sporadic and develop with age. Degenerative neural tissues often contain intra- and extracellular protein aggregates, suggesting that the proteostasis network that combats protein misfolding could be ...
Hisayo Jin, Mari Komita, Tomohiko Aoe
doaj   +1 more source

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