scholarly journals The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease

2011 ◽  
Vol 250 (3) ◽  
pp. 291-298 ◽  
Author(s):  
Qiujun Wang ◽  
Ge Liang ◽  
Hui Yang ◽  
Shouping Wang ◽  
Maryellen F. Eckenhoff ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Calcium Homeostasis ◽  
Cell Model ◽  
A Cell ◽  
The Common ◽  
Inhaled Anesthetic

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.

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.

scholarly journals Osmolytes dynamically regulate mutant Huntingtin aggregation and CREB function in Huntington’s disease cell models

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shreyaas Aravindan ◽  
Samantha Chen ◽  
Hannaan Choudhry ◽  
Celine Molfetta ◽  
Kuang Yu Chen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Inclusion Bodies ◽  
Cell Model ◽  
Mutant Huntingtin ◽  
Protein Protein Interaction ◽  
Intrinsically Disordered ◽  
Disease Protein ◽  
Disease Cell

Abstract Osmolytes are organic solutes that change the protein folding landscape shifting the equilibrium towards the folded state. Herein, we use osmolytes to probe the structuring and aggregation of the intrinsically disordered mutant Huntingtin (mHtt) vis-a-vis the pathogenicity of mHtt on transcription factor function and cell survival. Using an inducible PC12 cell model of Huntington’s disease (HD), we show that stabilizing polyol osmolytes drive the aggregation of Htt103QExon1-EGFP from a diffuse ensemble into inclusion bodies (IBs), whereas the destabilizing osmolyte urea does not. This effect of stabilizing osmolytes is innate, generic, countered by urea, and unaffected by HSP70 and HSC70 knockdown. A qualitatively similar result of osmolyte-induced mHtt IB formation is observed in a conditionally immortalized striatal neuron model of HD, and IB formation correlates with improved survival under stress. Increased expression of diffuse mHtt sequesters the CREB transcription factor to repress CREB-reporter gene activity. This repression is mitigated either by stabilizing osmolytes, which deplete diffuse mHtt or by urea, which negates protein–protein interaction. Our results show that stabilizing polyol osmolytes promote mHtt aggregation, alleviate CREB dysfunction, and promote survival under stress to support the hypothesis that lower molecular weight entities of disease protein are relevant pathogenic species in neurodegeneration.

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