Results 81 to 90 of about 82,738 (226)

Large‐scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of αSynuclein aggregation

FEBS Open Bio, EarlyView.
Activation of the mitochondrial protein OXR1 increases pSyn129 αSynuclein aggregation by lowering ATP levels and altering mitochondrial membrane potential, particularly in response to MSA‐derived fibrils. In contrast, ablation of the ER protein EMC4 enhances autophagic flux and lysosomal clearance, broadly reducing α‐synuclein aggregates.
Sandesh Neupane, Lea Nikolić, Lorenzo Maraio, Thomas Goiran, Nathan Karpilovsky, Stefano Sellitto, Vangelis Bouris, Jiang‐An Yin, Ronald Melki, Edward A Fon, Adriano Aguzzi, Elena De Cecco   +11 more
wiley   +1 more source

Structural and Dynamical Properties of Nucleic Acid Hairpins Implicated in Trinucleotide Repeat Expansion Diseases

Biomolecules
Dynamic mutations in some human genes containing trinucleotide repeats are associated with severe neurodegenerative and neuromuscular disorders—known as Trinucleotide (or Triplet) Repeat Expansion Diseases (TREDs)—which arise when the repeat number of ...
Feng Pan, Pengning Xu, Christopher Roland, Celeste Sagui, Keith Weninger   +4 more
doaj   +1 more source

Base excision repair of chemotherapeutically-induced alkylated DNA damage predominantly causes contractions of expanded GAA repeats associated with Friedreich's ataxia.

PLoS ONE, 2014
Expansion of GAA·TTC repeats within the first intron of the frataxin gene is the cause of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disorder. However, no effective treatment for the disease has been developed as yet.
Yanhao Lai, Jill M Beaver, Karla Lorente, Jonathan Melo, Shyama Ramjagsingh, Irina U Agoulnik, Zunzhen Zhang, Yuan Liu   +7 more
doaj   +1 more source

Identifying transcription factors controlling the basal expression of human MRP4 highlights a substantial role for Sp1

FEBS Open Bio, EarlyView.
The MRP4 transporter exports several drugs and signaling molecules. Here, we identified key promoter elements regulating basal MRP4 expression. Using reporter assays, we defined a conserved region with essential Sp1 and contributory Ets sites, which controlled basal MRP4 expression.
Debora Singer, Angelique Kragl, Katrin Ziems, Juliane Glaubitz, Sophie Grammbauer, Susanne Hildebrandt, Mladen V. Tzvetkov, Gabriele Jedlitschky   +7 more
wiley   +1 more source

A Potential Role for TLR9 Dysfunction in the Pathogenesis and Progression of Repeat Expansion Disorders [PDF]

Expansions of unstable DNA repeats in the human genome give rise to neurological disorders, but the mechanisms linking high numbers of DNA repeats to disease pathogenesis are not completely understood. The innate immunoreceptor toll-like receptor 9 (TLR9)
Cohen, SJ
core  

Mechanism of trinucleotide repeat expansion by MutSβ-MutLγ and contraction by FAN1

Nature Communications
Triplet repeat expansion underlies multiple pathologies, including Huntington’s disease, often arising in somatic non-dividing tissues such as the brain. Despite identification of genetic modifiers, mechanistic insights remain limited.
Issam Senoussi, Valentina Mengoli, Arianna Cerana, Andrea Rinaldi, Andrés Marco, Giordano Reginato, Simone G. Moro, Ananya Acharya, Megha Roy, Akshay Jayachandran, Elda Cannavo, Ilaria Ceppi, Petr Cejka   +12 more
doaj   +1 more source

Twisting right to left: A…A mismatch in a CAG trinucleotide repeat overexpansion provokes left-handed Z-DNA conformation.

PLoS Computational Biology, 2015
Conformational polymorphism of DNA is a major causative factor behind several incurable trinucleotide repeat expansion disorders that arise from overexpansion of trinucleotide repeats located in coding/non-coding regions of specific genes.
Noorain Khan, Narendar Kolimi, Thenmalarchelvi Rathinavelan   +2 more
doaj   +1 more source

Derivation and characterization of retinal pigment epithelium from urine‐derived iPSCs

FEBS Open Bio, EarlyView.
Age‐related macular degeneration causes vision loss via RPE dysfunction and loss. Traditional iPSC therapies rely on invasive biopsies, limiting scalability. Here, we utilize urine‐derived stem cells as an accessible source to generate u‐iPSCs, successfully differentiated into pigmented RPE. This “Urine‐to‐Retina” platform provides a promising path for
Daniella Beiner, Hainan Zhu, Carol Christine Bosholm, Heuy‐Ching Wang, Tracy Criswell, Anthony Atala, Jian‐Xing Ma, Yuanyuan Zhang   +7 more
wiley   +1 more source

Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion

Molecular Neurodegeneration
Background The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia.
Evan Udine, NiCole A. Finch, Mariely DeJesus-Hernandez, Jazmyne L. Jackson, Matthew C. Baker, Siva Arumugam Saravanaperumal, Eric Wieben, Mark T.W. Ebbert, Jaimin Shah, Leonard Petrucelli, Rosa Rademakers, Björn Oskarsson, Marka van Blitterswijk   +12 more
doaj   +1 more source

Pharmacological inhibition of the PERK pathway modulates hepatocellular carcinoma growth and immune signaling

FEBS Open Bio, EarlyView.
Pharmacological inhibition of PERK in a DEN‐induced mouse model of liver cancer does not reduce tumor burden but alters cellular stress signaling. Despite blocking PERK activity, downstream stress responses, including CHOP expression, remain active, suggesting compensatory mechanisms within the unfolded protein response that may influence tumor ...
Ada Lerma‐Clavero, Maria Kopsida, Nathalie Arendt, Hans Lennernäs, Markus Sjöblom, Femke Heindryckx   +5 more
wiley   +1 more source