scholarly journals Calcium Handling by Endoplasmic Reticulum and Mitochondria in a Cell Model of Huntington’s Disease

PLoS Currents ◽  
2016 ◽  
Author(s):  
Agnese De Mario ◽  
Chiara Scarlatti ◽  
Veronica Costiniti ◽  
Simona Primerano ◽  
Raffaele Lopreiato ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cell Model ◽  
Calcium Handling ◽  
A Cell

scholarly journals Regulation of miR-146a by RelA/NFkB and p53 in STHdhQ111/HdhQ111 Cells, a Cell Model of Huntington's Disease

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23837 ◽  
Author(s):  
Jayeeta Ghose ◽  
Mithun Sinha ◽  
Eashita Das ◽  
Nihar R. Jana ◽  
Nitai P. Bhattacharyya
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cell Model ◽  
A Cell

scholarly journals The Novel Alpha-2 Adrenoceptor Inhibitor Beditin Reduces Cytotoxicity and Huntingtin Aggregates in Cell Models of Huntington’s Disease

2021 ◽  
Vol 14 (3) ◽  
pp. 257
Author(s):  
Elisabeth Singer ◽  
Lilit Hunanyan ◽  
Magda M. Melkonyan ◽  
Jonasz J. Weber ◽  
Lusine Danielyan ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Cell Model ◽  
Resonance Energy Transfer ◽  
Neuronal Cell ◽  
Resonance Energy ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Cell Models

Huntington’s disease (HD) is a monogenetic neurodegenerative disorder characterized by the accumulation of polyglutamine-expanded huntingtin (mHTT). There is currently no cure, and therefore disease-slowing remedies are sought to alleviate symptoms of the multifaceted disorder. Encouraging findings in Alzheimer’s and Parkinson’s disease on alpha-2 adrenoceptor (α2-AR) inhibition have shown neuroprotective and aggregation-reducing effects in cell and animal models. Here, we analyzed the effect of beditin, a novel α2- adrenoceptor (AR) antagonist, on cell viability and mHTT protein levels in cell models of HD using Western blot, time-resolved Foerster resonance energy transfer (TR-FRET), lactate dehydrogenase (LDH) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) cytotoxicity assays. Beditin decreases cytotoxicity, as measured by TUNEL staining and LDH release, in a neuronal progenitor cell model (STHdh cells) of HD and decreases the aggregation propensity of HTT exon 1 fragments in an overexpression model using human embryonic kidney (HEK) 293T cells. α2-AR is a promising therapeutic target for further characterization in HD models. Our data allow us to suggest beditin as a valuable candidate for the pharmaceutical manipulation of α2-AR, as it is capable of modulating neuronal cell survival and the level of mHTT.

Changes in PUFA Levels and Inflammation in a Cell Model of Hepatic Endoplasmic Reticulum Stress

2017 ◽  
Vol 112 ◽  
pp. 199
Author(s):  
Mutay Aslan ◽  
Ebru Kirac ◽  
Ozlem Yılmaz ◽  
Esma Kirimlioglu Konuk ◽  
Filiz Ozcan
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Model ◽  
A Cell

scholarly journals Endoplasmic reticulum stress induces a novel Ca2+ signalling system initiated by Ca2+ microdomains

2020 ◽  
Author(s):  
Constanza Feliziani ◽  
Gonzalo Quasollo ◽  
Deborah Holstein ◽  
Macarena Fernandez ◽  
James C Paton ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Model ◽  
Signal Transduction Pathway ◽  
Unfolded Proteins ◽  
Potent Inducer ◽  
Human Astrocytes ◽  
Receptor Isoforms ◽  
A Cell ◽  
Er Homeostasis

AbstractThe accumulation of unfolded proteins within the Endoplasmic Reticulum (ER) activates a signal transduction pathway termed the unfolded protein response (UPR), which attempts to restore ER homeostasis. If homeostasis cannot be restored, UPR signalling ultimately induces apoptosis. Ca2+ depletion in the ER is a potent inducer of ER stress. Despite the ubiquity of Ca2+ as intracellular messenger, the precise mechanism (s) by which Ca2+ release affects the UPR remains unknown. Use of a genetically encoded Ca2+ indicator (GCamP6) that is tethered to the ER membrane, uncovered novel Ca2+ signalling events initiated by Ca2+ microdomains in human astrocytes under ER stress, as well as in a cell model deficient in all three IP3 Receptor isoforms. Pharmacological and molecular studies indicate that these local events are mediated by translocons. Together, these data reveal the existence of a previously unrecognized mechanism by which stressor-mediated Ca2+ release regulates ER stress.

scholarly journals Huntington’s disease: Neural dysfunction linked to inositol polyphosphate multikinase

2015 ◽  
Vol 112 (31) ◽  
pp. 9751-9756 ◽  
Author(s):  
Ishrat Ahmed ◽  
Juan I. Sbodio ◽  
Maged M. Harraz ◽  
Richa Tyagi ◽  
Jonathan C. Grima ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Kinase Activity ◽  
Inositol Phosphate ◽  
Cell Model ◽  
Inositol Polyphosphate ◽  
Interacting Protein ◽  
Lipid Kinase ◽  
Inositol Polyphosphate Multikinase ◽  
Neural Dysfunction

Huntington’s disease (HD) is a progressive neurodegenerative disease caused by a glutamine repeat expansion in mutant huntingtin (mHtt). Despite the known genetic cause of HD, the pathophysiology of this disease remains to be elucidated. Inositol polyphosphate multikinase (IPMK) is an enzyme that displays soluble inositol phosphate kinase activity, lipid kinase activity, and various noncatalytic interactions. We report a severe loss of IPMK in the striatum of HD patients and in several cellular and animal models of the disease. This depletion reflects mHtt-induced impairment of COUP-TF-interacting protein 2 (Ctip2), a striatal-enriched transcription factor for IPMK, as well as alterations in IPMK protein stability. IPMK overexpression reverses the metabolic activity deficit in a cell model of HD. IPMK depletion appears to mediate neural dysfunction, because intrastriatal delivery of IPMK abates the progression of motor abnormalities and rescues striatal pathology in transgenic murine models of HD.

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