scholarly journals The pathobiology of perturbed mutant huntingtin protein–protein interactions in Huntington's disease

2019 ◽  
Vol 151 (4) ◽  
pp. 507-519 ◽  
Author(s):  
Erich E. Wanker ◽  
Anne Ast ◽  
Franziska Schindler ◽  
Philipp Trepte ◽  
Sigrid Schnoegl
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Protein Interactions ◽  
Mutant Huntingtin ◽  
Protein Protein Interactions ◽  
Huntingtin Protein ◽  
Mutant Huntingtin Protein

scholarly journals The huntingtin inclusion is a dynamic phase-separated compartment

2019 ◽  
Vol 2 (5) ◽  
pp. e201900489 ◽  
Author(s):  
Fahmida Aktar ◽  
Chakkapong Burudpakdee ◽  
Mercedes Polanco ◽  
Sen Pei ◽  
Theresa C Swayne ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Vacuolar Membrane ◽  
Mutant Huntingtin ◽  
Small Particles ◽  
Huntingtin Protein ◽  
Disordered Protein ◽  
Dynamic Phase ◽  
Mutant Huntingtin Protein ◽  
Polyglutamine Tract

Inclusions of disordered protein are a characteristic feature of most neurodegenerative diseases, including Huntington’s disease. Huntington’s disease is caused by expansion of a polyglutamine tract in the huntingtin protein; mutant huntingtin protein (mHtt) is unstable and accumulates in large intracellular inclusions both in affected individuals and when expressed in eukaryotic cells. Using mHtt-GFP expressed in Saccharomyces cerevisiae, we find that mHtt-GFP inclusions are dynamic, mobile, gel-like structures that concentrate mHtt together with the disaggregase Hsp104. Although inclusions may associate with the vacuolar membrane, the association is reversible and we find that inclusions of mHtt in S. cerevisiae are not taken up by the vacuole or other organelles. Instead, a pulse-chase study using photoconverted mHtt-mEos2 revealed that mHtt is directly and continuously removed from the inclusion body. In addition to mobile inclusions, we also imaged and tracked the movements of small particles of mHtt-GFP and determine that they move randomly. These observations suggest that inclusions may grow through the collision and coalescence of small aggregative particles.

scholarly journals Striatal Mutant Huntingtin Protein Levels Decline with Age in Homozygous Huntington’s Disease Knock-In Mouse Models

2018 ◽  
Vol 7 (2) ◽  
pp. 137-150 ◽  
Author(s):  
Nicholas R. Franich ◽  
Manuela Basso ◽  
Emily A. André ◽  
Joseph Ochaba ◽  
Amit Kumar ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Mutant Huntingtin ◽  
Huntingtin Protein ◽  
Protein Levels ◽  
Mutant Huntingtin Protein

scholarly journals Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ismael Al-Ramahi ◽  
Sai Srinivas Panapakkam Giridharan ◽  
Yu-Chi Chen ◽  
Samarjit Patnaik ◽  
Nathaniel Safren ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Selective Inhibition ◽  
Mutant Huntingtin ◽  
Causative Gene ◽  
Human Patient ◽  
Lipid Kinase ◽  
Huntingtin Protein ◽  
Mutant Huntingtin Protein ◽  
A Cell

The discovery of the causative gene for Huntington’s disease (HD) has promoted numerous efforts to uncover cellular pathways that lower levels of mutant huntingtin protein (mHtt) and potentially forestall the appearance of HD-related neurological defects. Using a cell-based model of pathogenic huntingtin expression, we identified a class of compounds that protect cells through selective inhibition of a lipid kinase, PIP4Kγ. Pharmacological inhibition or knock-down of PIP4Kγ modulates the equilibrium between phosphatidylinositide (PI) species within the cell and increases basal autophagy, reducing the total amount of mHtt protein in human patient fibroblasts and aggregates in neurons. In two Drosophila models of Huntington’s disease, genetic knockdown of PIP4K ameliorated neuronal dysfunction and degeneration as assessed using motor performance and retinal degeneration assays respectively. Together, these results suggest that PIP4Kγ is a druggable target whose inhibition enhances productive autophagy and mHtt proteolysis, revealing a useful pharmacological point of intervention for the treatment of Huntington’s disease, and potentially for other neurodegenerative disorders.

Ellagic acid rescues motor and cognitive deficits in the R6/2 mouse model of Huntington's disease by lowering mutant huntingtin protein

2020 ◽  
Vol 11 (2) ◽  
pp. 1334-1348 ◽  
Author(s):  
Xun Sun ◽  
Jie Zhu ◽  
Xiao-ying Sun ◽  
Mei Ji ◽  
Xiao-lin Yu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cognitive Deficits ◽  
Ellagic Acid ◽  
Mutant Huntingtin ◽  
Huntingtin Protein ◽  
Mutant Huntingtin Protein

Ellagic acid significantly attenuated motor and cognitive deficits and ameliorated neuropathological features in the R6/2 mouse model of Huntington's disease.

Huntington’s Disease and Mitochondrial DNA Deletions: Event or Regular Mechanism for Mutant Huntingtin Protein and CAG Repeats Expansion?!

2007 ◽  
Vol 27 (7) ◽  
pp. 867-875 ◽  
Author(s):  
Mohammad Mehdi Banoei ◽  
Massoud Houshmand ◽  
Mehdi Shafa Shariat Panahi ◽  
Parvin Shariati ◽  
Maryam Rostami ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cag Repeats ◽  
Mutant Huntingtin ◽  
Huntingtin Protein ◽  
Dna Deletions ◽  
Mutant Huntingtin Protein

scholarly journals Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington’s disease patients

2015 ◽  
Vol 125 (5) ◽  
pp. 1979-1986 ◽  
Author(s):  
Edward J. Wild ◽  
Roberto Boggio ◽  
Douglas Langbehn ◽  
Nicola Robertson ◽  
Salman Haider ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mutant Huntingtin ◽  
Huntingtin Protein ◽  
Mutant Huntingtin Protein
Sign in / Sign up

Export Citation Format

Share Document