A link between chromatin condensation mechanisms and Huntington's disease: connecting the dots

2016 ◽  
Vol 12 (12) ◽  
pp. 3515-3529 ◽  
Author(s):  
Sonali Lokhande ◽  
Biranchi N. Patra ◽  
Animesh Ray
Keyword(s):  
Dna Damage ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Chromatin Condensation ◽  
Chromosome Condensation ◽  
Molecular Pathogenesis ◽  
Neural Degeneration ◽  
Connecting The Dots

This review highlights the molecular pathogenesis of Huntington's disease emphasizing how chromosome condensation defects and DNA damage may cause neural degeneration.

scholarly journals N6-Furfuryladenine is protective in Huntington’s disease models by signaling huntingtin phosphorylation

2018 ◽  
Vol 115 (30) ◽  
pp. E7081-E7090 ◽  
Author(s):  
Laura E. Bowie ◽  
Tamara Maiuri ◽  
Melanie Alpaugh ◽  
Michelle Gabriel ◽  
Nicolas Arbez ◽  
...  
Keyword(s):  
Dna Damage ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Oxidative Dna Damage ◽  
Model Systems ◽  
Protective Effects ◽  
Mutant Huntingtin ◽  
Naturally Occurring ◽  
Phosphate Donor ◽  
High Content Analysis

The huntingtin N17 domain is a modulator of mutant huntingtin toxicity and is hypophosphorylated in Huntington’s disease (HD). We conducted high-content analysis to find compounds that could restore N17 phosphorylation. One lead compound from this screen was N6-furfuryladenine (N6FFA). N6FFA was protective in HD model neurons, and N6FFA treatment of an HD mouse model corrects HD phenotypes and eliminates cortical mutant huntingtin inclusions. We show that N6FFA restores N17 phosphorylation levels by being salvaged to a triphosphate form by adenine phosphoribosyltransferase (APRT) and used as a phosphate donor by casein kinase 2 (CK2). N6FFA is a naturally occurring product of oxidative DNA damage. Phosphorylated huntingtin functionally redistributes and colocalizes with CK2, APRT, and N6FFA DNA adducts at sites of induced DNA damage. We present a model in which this natural product compound is salvaged to provide a triphosphate substrate to signal huntingtin phosphorylation via CK2 during low-ATP stress under conditions of DNA damage, with protective effects in HD model systems.

scholarly journals Deregulation of BRCA1 Leads to Impaired Spatiotemporal Dynamics of γ-H2AX and DNA Damage Responses in Huntington’s Disease

2012 ◽  
Vol 45 (3) ◽  
pp. 550-563 ◽  
Author(s):  
Gye Sun Jeon ◽  
Ki Yoon Kim ◽  
Yu Jin Hwang ◽  
Min-Kyung Jung ◽  
Sungkwan An ◽  
...  
Keyword(s):  
Dna Damage ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Spatiotemporal Dynamics ◽  
Dna Damage Responses

D6 Dna damage in lymphocytes as a predictor of illness evolution in pre-manifest and overt huntington’s disease

2016 ◽  
Vol 87 (Suppl 1) ◽  
pp. A35.3-A36
Author(s):  
Michela Ferraldeschi ◽  
Silvia Romano ◽  
A Delmondo ◽  
A Monaco ◽  
Maria Spadaro ◽  
...  
Keyword(s):  
Dna Damage ◽  
Huntington's Disease ◽  
Huntington’S Disease

DNA Damage Signatures in Peripheral Blood Cells as Biomarkers in Prodromal Huntington's Disease

2018 ◽  
Author(s):  
Imma Castaldo ◽  
Mariarosaria De Rosa ◽  
Antonella Romano ◽  
Candida Zuchegna ◽  
Ferdinando Squitieri ◽  
...  
Keyword(s):  
Dna Damage ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Peripheral Blood Cells

scholarly journals Mitochondrial DNA damage Is associated with reduced mitochondrial bioenergetics in Huntington's disease

2012 ◽  
Vol 53 (7) ◽  
pp. 1478-1488 ◽  
Author(s):  
Almas Siddiqui ◽  
Sulay Rivera-Sánchez ◽  
María del R. Castro ◽  
Karina Acevedo-Torres ◽  
Anand Rane ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mitochondrial Bioenergetics ◽  
Mitochondrial Dna Damage
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