Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)‐binding protein 1 in Huntington's disease

2019 ◽  
Vol 39 (5) ◽  
pp. 358-367 ◽  
Author(s):  
Shinichiro Mori ◽  
Hiroyuki Honda ◽  
Takashi Ishii ◽  
Motoi Yoshimura ◽  
Naokazu Sasagasako ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Binding Protein ◽  
Nuclear Distribution ◽  
Fused In Sarcoma

scholarly journals Investigating the Transition of Pre-Symptomatic to Symptomatic Huntington’s Disease Status Based on Omics Data

2020 ◽  
Vol 21 (19) ◽  
pp. 7414
Author(s):  
Christiana C. Christodoulou ◽  
Margarita Zachariou ◽  
Marios Tomazou ◽  
Evangelos Karatzas ◽  
Christiana A. Demetriou ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Transforming Growth Factor Beta ◽  
Kinase Activity ◽  
Transforming Growth Factor ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Binding Protein ◽  
Biological Data ◽  
Disease Stage

Huntington’s disease is a rare neurodegenerative disease caused by a cytosine–adenine–guanine (CAG) trinucleotide expansion in the Huntingtin (HTT) gene. Although Huntington’s disease (HD) is well studied, the pathophysiological mechanisms, genes and metabolites involved in HD remain poorly understood. Systems bioinformatics can reveal synergistic relationships among different omics levels and enables the integration of biological data. It allows for the overall understanding of biological mechanisms, pathways, genes and metabolites involved in HD. The purpose of this study was to identify the differentially expressed genes (DEGs), pathways and metabolites as well as observe how these biological terms differ between the pre-symptomatic and symptomatic HD stages. A publicly available dataset from the Gene Expression Omnibus (GEO) was analyzed to obtain the DEGs for each HD stage, and gene co-expression networks were obtained for each HD stage. Network rewiring, highlights the nodes that change most their connectivity with their neighbors and infers their possible implication in the transition between different states. The CACNA1I gene was the mostly highly rewired node among pre-symptomatic and symptomatic HD network. Furthermore, we identified AF198444 to be common between the rewired genes and DEGs of symptomatic HD. CNTN6, DEK, LTN1, MST4, ZFYVE16, CEP135, DCAKD, MAP4K3, NUPL1 and RBM15 between the DEGs of pre-symptomatic and DEGs of symptomatic HD and CACNA1I, DNAJB14, EPS8L3, HSDL2, SNRPD3, SOX12, ACLY, ATF2, BAG5, ERBB4, FOCAD, GRAMD1C, LIN7C, MIR22, MTHFR, NABP1, NRG2, OTC, PRAMEF12, SLC30A10, STAG2 and Y16709 between the rewired genes and DEGs of pre-symptomatic HD. The proteins encoded by these genes are involved in various biological pathways such as phosphatidylinositol-4,5-bisphosphate 3-kinase activity, cAMP response element-binding protein binding, protein tyrosine kinase activity, voltage-gated calcium channel activity, ubiquitin protein ligase activity, adenosine triphosphate (ATP) binding, and protein serine/threonine kinase. Additionally, prominent molecular pathways for each HD stage were then obtained, and metabolites related to each pathway for both disease stages were identified. The transforming growth factor beta (TGF-β) signaling (pre-symptomatic and symptomatic stages of the disease), calcium (Ca2+) signaling (pre-symptomatic), dopaminergic synapse pathway (symptomatic HD patients) and Hippo signaling (pre-symptomatic) pathways were identified. The in silico metabolites we identified include Ca2+, inositol 1,4,5-trisphosphate, sphingosine 1-phosphate, dopamine, homovanillate and L-tyrosine. The genes, pathways and metabolites identified for each HD stage can provide a better understanding of the mechanisms that become altered in each disease stage. Our results can guide the development of therapies that may target the altered genes and metabolites of the perturbed pathways, leading to an improvement in clinical symptoms and hopefully a delay in the age of onset.

scholarly journals Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease

2014 ◽  
Vol 24 (6) ◽  
pp. 1563-1573 ◽  
Author(s):  
Laetitia Francelle ◽  
Laurie Galvan ◽  
Marie-Claude Gaillard ◽  
Martine Guillermier ◽  
Diane Houitte ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Binding Protein ◽  
Mutant Huntingtin ◽  
Striatal Neurons ◽  
Hormone Binding ◽  
Hormone Binding Protein

Insoluble TATA-binding protein accumulation in Huntington’s disease cortex

2002 ◽  
Vol 109 (1-2) ◽  
pp. 1-10 ◽  
Author(s):  
Willeke M.C van Roon-Mom ◽  
Suzanne J Reid ◽  
A.Lesley Jones ◽  
Marcy E MacDonald ◽  
Richard L.M Faull ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Binding Protein ◽  
Tata Binding Protein ◽  
Protein Accumulation

LOSS OF MATRIX CALCIUM-BINDING PROTEIN-CONTAINING NEURONS IN HUNTINGTON'S DISEASE

The Lancet ◽  
1988 ◽  
Vol 331 (8597) ◽  
pp. 1252-1255 ◽  
Author(s):  
A. Seto-Ohshima ◽  
E. Lawson ◽  
P.C. Emson ◽  
C.Q. Mountjoy ◽  
L.H. Carrasco
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Calcium Binding ◽  
Binding Protein ◽  
Calcium Binding Protein

scholarly journals The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription

2000 ◽  
Vol 97 (12) ◽  
pp. 6763-6768 ◽  
Author(s):  
J. S. Steffan ◽  
A. Kazantsev ◽  
O. Spasic-Boskovic ◽  
M. Greenwald ◽  
Y.-Z. Zhu ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Binding Protein ◽  
Creb Binding Protein ◽  
Disease Protein
Sign in / Sign up

Export Citation Format

Share Document