scholarly journals Modern approaches for modelling dystonia and Huntington's disease in vitro and in vivo

2019 ◽  
Vol 100 (2) ◽  
pp. 64-71
Author(s):  
Olga A. Zhunina ◽  
Nikita G. Yabbarov ◽  
Alexander N. Orekhov ◽  
Alexey V. Deykin
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease

scholarly journals Cerebral dopamine neurotrophic factor (CDNF) protects against quinolinic acid-induced toxicity in in vitro and in vivo models of Huntington’s disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
P. Stepanova ◽  
V. Srinivasan ◽  
D. Lindholm ◽  
M. H. Voutilainen
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Quinolinic Acid ◽  
Neurotrophic Factor ◽  
Striatal Neurons ◽  
In Vivo Models ◽  
Cerebral Dopamine Neurotrophic Factor ◽  
Cerebral Dopamine

Abstract Huntington’s disease (HD) is a neurodegenerative disorder with a progressive loss of medium spiny neurons in the striatum and aggregation of mutant huntingtin in the striatal and cortical neurons. Currently, there are no rational therapies for the treatment of the disease. Cerebral dopamine neurotrophic factor (CDNF) is an endoplasmic reticulum (ER) located protein with neurotrophic factor (NTF) properties, protecting and restoring the function of dopaminergic neurons in animal models of PD more effectively than other NTFs. CDNF is currently in phase I–II clinical trials on PD patients. Here we have studied whether CDNF has beneficial effects on striatal neurons in in vitro and in vivo models of HD. CDNF was able to protect striatal neurons from quinolinic acid (QA)-induced cell death in vitro via increasing the IRE1α/XBP1 signalling pathway in the ER. A single intrastriatal CDNF injection protected against the deleterious effects of QA in a rat model of HD. CDNF improved motor coordination and decreased ataxia in QA-toxin treated rats, and stimulated the neurogenesis by increasing doublecortin (DCX)-positive and NeuN-positive cells in the striatum. These results show that CDNF positively affects striatal neuron viability reduced by QA and signifies CDNF as a promising drug candidate for the treatment of HD.

scholarly journals The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum–microglia crosstalk preventing disease progression in a mouse model of Huntington’s disease

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Alba Di Pardo ◽  
Elena Ciaglia ◽  
Monica Cattaneo ◽  
Anna Maciag ◽  
Francesco Montella ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Motor Dysfunction ◽  
Cag Repeats ◽  
Huntingtin Protein ◽  
Human Microglia

Abstract The longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been found significantly enriched in long-living individuals. Neuroinflammation is a key player in Huntington’s disease (HD), a neurodegenerative disorder caused by neural death due to expanded CAG repeats encoding a long polyglutamine tract in the huntingtin protein (Htt). Herein, we showed that striatal-derived cell lines with expanded Htt (STHdh Q111/111) expressed and secreted lower levels of BPIFB4, when compared with Htt expressing cells (STHdh Q7/7), which correlated with a defective stress response to proteasome inhibition. Overexpression of LAV-BPIFB4 in STHdh Q111/111 cells was able to rescue both the BPIFB4 secretory profile and the proliferative/survival response. According to a well-established immunomodulatory role of LAV-BPIFB4, conditioned media from LAV-BPIFB4-overexpressing STHdh Q111/111 cells were able to educate Immortalized Human Microglia—SV40 microglial cells. While STHdh Q111/111 dying cells were ineffective to induce a CD163 + IL-10high pro-resolving microglia compared to normal STHdh Q7/7, LAV-BPIFB4 transduction promptly restored the central immune control through a mechanism involving the stromal cell-derived factor-1. In line with the in vitro results, adeno-associated viral-mediated administration of LAV-BPIFB4 exerted a CXCR4-dependent neuroprotective action in vivo in the R6/2 HD mouse model by preventing important hallmarks of the disease including motor dysfunction, body weight loss, and mutant huntingtin protein aggregation. In this view, LAV-BPIFB4, due to its pleiotropic ability in both immune compartment and cellular homeostasis, may represent a candidate for developing new treatment for HD.

scholarly journals Huntington's disease: from gene to potential therapy

2001 ◽  
Vol 3 (1) ◽  
pp. 17-23
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Western Europe ◽  
Molecular Mechanisms ◽  
Late Onset ◽  
Cell Metabolism ◽  
Normal Function ◽  
Model Systems

Huntington's disease (HD) is a progressive, late-onset neurodegenerative illness with autosomal dominant inheritance that affects one in 10 000 individuals in Western Europe. The disease is caused by a polyglutamine repeat expansion located in the N-terminal region of the huntingtin protein. The mutation is likely to act by a gain of function, but the molecular mechanisms by which it leads to neuronal dysfunction and cell death are not yet known. The normal function of huntingtin in cell metabolism is also unclear. There is no therapy for HD. Research on HD should help elucidate the pathogenetic mechanism of this illness in order to develop successful treatments to prevent or slow down symptoms. This article presents new results in HD research focusing on in vivo and in vitro model systems, potential molecular mechanisms of HD, and the development of therapeutic strategies.

scholarly journals Pizotifen Activates ERK and Provides Neuroprotection in vitro and in vivo in Models of Huntington's Disease

2012 ◽  
Vol 1 (2) ◽  
pp. 195-210 ◽  
Author(s):  
Melissa R. Sarantos ◽  
Theodora Papanikolaou ◽  
Lisa M. Ellerby ◽  
Robert E. Hughes
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease

scholarly journals VGF and striatal cell damage in in vitro and in vivo models of Huntington's disease

2015 ◽  
Vol 3 (3) ◽  
Author(s):  
Yasuhiro Noda ◽  
Masamitsu Shimazawa ◽  
Hirotaka Tanaka ◽  
Shigeki Tamura ◽  
Teruyoshi Inoue ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cell Damage ◽  
In Vivo Models
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