Adenovirus vector-based in vitro neuronal cell model for Huntington's disease with human disease-like differential aggregation and degeneration

2012 ◽  
Vol 14 (7) ◽  
pp. 468-481 ◽  
Author(s):  
Xiaomin Dong ◽  
Shan Zong ◽  
Anke Witting ◽  
Katrin S. Lindenberg ◽  
Stefan Kochanek ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Human Disease ◽  
Cell Model ◽  
Neuronal Cell ◽  
Adenovirus Vector

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 Potential application of grape derived polyphenols in Huntington’s disease

2010 ◽  
Vol 1 (2) ◽  
Author(s):  
Jun Wang ◽  
Cathie Pfleger ◽  
Lauren Friedman ◽  
Roselle Vittorino ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Feasibility Studies ◽  
Grape Seed ◽  
Polyphenolic Extract

AbstractHuntington’s disease (HD) is a progressive neurodegenerative disorder associated with selective neuronal cell death. Abnormal aggregation of huntingtin protein with polyQ expansion has been shown to be causally linked to HD. Grape seed polyphenolic extract (GSPE) is a natural compound that has previously been shown to interfere with aggregations of proteins involved in neurological disorders, such as amyloid beta peptides (Aβ) and Tau protein. In this study we found that GSPE treatment significantly inhibits polyQ aggregation in phaeochromocytoma (PC)-12 cell line containing an ecdysone-inducible protein comprising the first 17 amino acid of huntingtin plus 103 glutamines fused with enhanced GFP. In vivo feasibility studies using the Q93httexon1 drosophila model of HD, we extended our in vitro evidence and found that flies fed with GSPE had a significantly improved lifespan compared to the control flies. Using the R6/2 rodent model of HD, we found that oral administration of 100 mg/kg/day GSPE (equivalent to 500mg per day in human) significantly attenuated the motor skill decay as well as extended the lifespan in the R6/2 mice relative to vehicle-control mice. Collectively, our studies strongly suggest that GSPE might be able to modulate the onset and/or progression of HD.

Compounds blocking mutant huntingtin toxicity identified using a Huntington's disease neuronal cell model

2005 ◽  
Vol 20 (2) ◽  
pp. 500-508 ◽  
Author(s):  
Wenfei Wang ◽  
Wenzhen Duan ◽  
Shuichi Igarashi ◽  
Hokuto Morita ◽  
Masayuki Nakamura ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cell Model ◽  
Neuronal Cell ◽  
Mutant Huntingtin

Copper dyshomoeostasis in Parkinson's disease: implications for pathogenesis and indications for novel therapeutics

2016 ◽  
Vol 130 (8) ◽  
pp. 565-574 ◽  
Author(s):  
Katherine M. Davies ◽  
Julian F.B. Mercer ◽  
Nicholas Chen ◽  
Kay L. Double
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuronal Degeneration ◽  
Large Body ◽  
Neuronal Cell ◽  
Normal Brain ◽  
In Vivo Models

Copper is a biometal essential for normal brain development and function, thus copper deficiency or excess results in central nervous system disease. Well-characterized disorders of disrupted copper homoeostasis with neuronal degeneration include Menkes disease and Wilson's disease but a large body of evidence also implicates disrupted copper pathways in other neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease and prion diseases. In this short review we critically evaluate the data regarding changes in systemic and brain copper levels in Parkinson's disease, where alterations in brain copper are associated with regional neuronal cell death and disease pathology. We review copper regulating mechanisms in the human brain and the effects of dysfunction within these systems. We then examine the evidence for a role for copper in pathogenic processes in Parkinson's disease and consider reports of diverse copper-modulating strategies in in vitro and in vivo models of this disorder. Copper-modulating therapies are currently advancing through clinical trials for Alzheimer's and Huntington's disease and may also hold promise as disease modifying agents in Parkinson's disease.

B01 In vitro study of neurodevelopment in huntington’s disease

2021 ◽  
Author(s):  
Phil Sanders ◽  
Waseem Abbas ◽  
Anna Esteve-Codina ◽  
Gustavo Rodriguez-Esteban ◽  
Georgina Bombau ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
In Vitro Study ◽  
Vitro Study

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
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