scholarly journals Modulation of nuclear REST by alternative splicing: a potential therapeutic target for Huntington's disease

2017 ◽  
Vol 21 (11) ◽  
pp. 2974-2984 ◽  
Author(s):  
Guo-Lin Chen ◽  
Qi Ma ◽  
Dharmendra Goswami ◽  
Jianyu Shang ◽  
Gregory M. Miller
Keyword(s):  
Alternative Splicing ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

The sigma 1 receptor (S1R) is a potential therapeutic target for the treatment of Huntington's disease

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Endoplasmic Reticulum ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Therapeutic Target ◽  
Structural Integrity ◽  
Neuronal Cell ◽  
Glutamate Excitotoxicity ◽  
Potential Therapeutic Target ◽  
Sigma 1 Receptor ◽  
Sigma 1

During the progression of Huntington's disease (HD), changes in Ca2+ signaling cause neuronal cells to lose a range of functional properties. GABAergic medium spiny neurons (MSNs) are able to prevent Ca2+ imbalance in the early stages of the illness through a number of compensatory strategies. However, as people become older, their neuroprotective potential diminishes due to a decrease in metabolic activity and the generation of Ca2+-buffering proteins. Continuing Ca2+ regulation problems exhaust the cells' compensatory abilities, resulting in a continuous surge in cytosolic Ca2+ and neuronal degeneration.The sigma 1 receptor (S1R) is a potential therapeutic target for the treatment of HD because it regulates a number of cytosolic Ca2+-dependent signaling cascades. S1R activation by selective agonists protects neurons from glutamate excitotoxicity, reduces store-operated Ca2+ entry (SOCE) hyperactivation, and maintains the structural integrity of mitochondria-associated endoplasmic reticulum membranes (MAMs), which is required for synchronizing mitochondrial and endoplasmic reticulum (ER) activity to maintain cell bioenergetics balance. Because of the stability of Ca2+ signaling in neurons, pridopidine, a highly selective S1R agonist, has been demonstrated to protect neurons in cellular and animal models of HD.The synaptoprotective effect of pridopidine is very important since it is found in both cortical and striatal neurons, indicating that pridopidine has a systemic influence on HD therapy. Because synaptic dysfunctions are one of the earliest markers of neuropathology at the cellular level, normalization of Ca2+ balance by pridopidine may prevent disease development at the molecular level at the earliest stages. In this regard, the most significant therapeutic advantage of pridopidine will almost certainly be in preventative treatment, even before the start of the first clinical indications, which will improve neuronal cell compensatory abilities and significantly reduce the progression of HD.

scholarly journals Mutant Huntingtin‐Calmodulin Interaction: Potential Therapeutic Target for Huntington's Disease

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Khushboo Kapadia ◽  
Anuradha Roy ◽  
Peter McDonald ◽  
Nicholas Klus ◽  
Kevin Frankowski ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Interaction Potential ◽  
Therapeutic Target ◽  
Mutant Huntingtin ◽  
Potential Therapeutic Target

scholarly journals Proteasome impairment does not contribute to pathogenesis in R6/2 Huntington's disease mice: exclusion of proteasome activator REGγ as a therapeutic target

2006 ◽  
Vol 15 (4) ◽  
pp. 665-665 ◽  
Author(s):  
John S. Bett ◽  
Geoffrey M. Goellner ◽  
Ben Woodman ◽  
Gregory Pratt ◽  
Martin Rechsteiner ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Therapeutic Target ◽  
Proteasome Activator

scholarly journals Mitochondrial calcium uptake capacity as a therapeutic target in the R6/2 mouse model of Huntington's disease

2010 ◽  
Vol 19 (17) ◽  
pp. 3354-3371 ◽  
Author(s):  
Giselle M. Perry ◽  
Sara Tallaksen-Greene ◽  
Ashish Kumar ◽  
Mary Y. Heng ◽  
Andrew Kneynsberg ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Therapeutic Target ◽  
Calcium Uptake ◽  
Mitochondrial Calcium ◽  
Uptake Capacity ◽  
Mitochondrial Calcium Uptake
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