The dawn of a new era for neurodegenerative disorders: Huntington's disease leading the way

2019 ◽  
Vol 34 (9) ◽  
pp. 1301-1302 ◽  
Author(s):  
Tiago A. Mestre ◽  
Mark Guttman
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorders ◽  
New Era ◽  
The Way

scholarly journals Curcumin-Loaded Nanoparticles Based on Amphiphilic Hyaluronan-Conjugate Explored as Targeting Delivery System for Neurodegenerative Disorders

2020 ◽  
Vol 21 (22) ◽  
pp. 8846
Author(s):  
Giuseppe Pepe ◽  
Enrica Calce ◽  
Valentina Verdoliva ◽  
Michele Saviano ◽  
Vittorio Maglione ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Delivery System ◽  
Neurodegenerative Disorders ◽  
Natural Polysaccharide ◽  
Promising Therapeutic Approach ◽  
Targeting Delivery ◽  
Effective Delivery ◽  
Vitro Model

Identification of molecules able to promote neuroprotective mechanisms can represent a promising therapeutic approach to neurodegenerative disorders including Huntington’s disease. Curcumin is an antioxidant and neuroprotective agent, even though its efficacy is limited by its poor absorption, rapid metabolism, systemic elimination, and limited blood–brain barrier (BBB) permeability. Herein, we report on novel biodegradable curcumin-containing nanoparticles to favor the compound delivery and potentially enhance its brain bioavailability. The prepared hyaluronan-based materials able to self-assemble in stable spherical nanoparticles, consist of natural fatty acids chemically conjugated to the natural polysaccharide. The aim of this study is to provide a possible effective delivery system for curcumin with the expectation that, after having released the drug at the specific site, the biopolymer can degrade to nontoxic fragments before renal excretion, since all the starting materials are provided by natural resource. Our findings demonstrate that curcumin-encapsulated nanoparticles enter the cells and reduce their susceptibility to apoptosis in an in vitro model of Huntington’s disease.

scholarly journals Huntington's Disease: Can Mice Lead the Way to Treatment?

Neuron ◽  
2011 ◽  
Vol 69 (5) ◽  
pp. 1038 ◽  
Author(s):  
Zachary R. Crook ◽  
David Housman
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
The Way

scholarly journals Astrocyte molecular signatures in Huntington’s disease

2019 ◽  
Vol 11 (514) ◽  
pp. eaaw8546 ◽  
Author(s):  
Blanca Diaz-Castro ◽  
Mohitkumar R. Gangwani ◽  
Xinzhu Yu ◽  
Giovanni Coppola ◽  
Baljit S. Khakh
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorders ◽  
Zinc Finger Protein ◽  
Disease Model ◽  
Core Gene ◽  
Molecular Signature ◽  
Transcriptional Repressors ◽  
Normal Functions ◽  
Mutant Huntingtin Protein

Astrocytes are implicated in neurodegenerative disorders and may contribute to striatal neuron loss or dysfunction in Huntington’s disease (HD). Here, we assessed striatal astrocyte gene and protein signatures in two HD mouse models at three stages and compared our results to human HD data at four clinical grades and to mice exhibiting polyglutamine length–dependent pathology. We found disease-model and stage-specific alterations and discovered a core disease-associated astrocyte molecular signature comprising 62 genes that were conserved between mice and humans. Our results show little evidence of neurotoxic A1 astrocytes that have been proposed to be causal for neuronal death in neurodegenerative disorders such as HD. Furthermore, 61 of the 62-core gene expression changes within astrocytes were reversed in a HD mouse model by lowering astrocyte mutant huntingtin protein (mHTT) expression using zinc finger protein (ZFP) transcriptional repressors. Our findings indicate that HD astrocytes progressively lose essential normal functions, some of which can be remedied by lowering mHTT. The data have implications for neurodegenerative disease rescue and repair strategies as well as specific therapeutic relevance for mHTT reduction and contribute to a better understanding of fundamental astrocyte biology and its contributions to disease.

Subcellular Pathology of Human Neurodegenerative Disorders: Alzheimer-Type Dementia and Huntington's Disease

2006 ◽  
Vol 47 (3) ◽  
pp. 882-889 ◽  
Author(s):  
A. J. Cross ◽  
T. J. Crow ◽  
J. M. Dawson ◽  
I. N. Ferrier ◽  
J. A. Johnson ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorders ◽  
Alzheimer Type ◽  
Alzheimer Type Dementia

scholarly journals Therapeutic and Mechanistic effects of Curcumin in Huntington’s disease

2020 ◽  
Vol 18 ◽  
Author(s):  
Fabiana Labanca ◽  
Hammad Ullah ◽  
Haroon Khan ◽  
Luigi Milella ◽  
Jianbo Xiao ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorders ◽  
Metal Ion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Autosomal Dominant Disorder ◽  
Therapeutic Choice ◽  
Transcriptional Alterations

: Curcumin is a spice derived nutraceutical which gained tremendous attention because of its profound medicinal values. It alters a number of molecular pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF‐κB), signal transducer and activator of transcription 3 (STAT3), nuclear factor erythroid 2-related factor 2 (Nrf2) and cyclooxygenases-2 (COX‐2), which make it potential therapeutic choice in treating multiple disorders. It also possesses potential to prevent protein aggregation and thus protect against degeneration of neurons in neurodegenerative disorders including Huntington’s disease (HD). HD is an autosomal dominant disorder linked with altered gene expression which leads to increase in size of cytosine, adenine and guanine (CAG) trinucleotide repeats, aids in protein aggregation throughout the brain and thus damages neurons. Upstream regulation of oxidative stress and inflammatory cascade are two important factors that drive HD progression. Available therapies just suppress the severity of symptoms with a number of side effects. Curcumin targets multiple mechanisms in treating or preventing HD including antioxidant and antiinflammatory potential, metal ion chelation, transcriptional alterations and upregulating activity of molecular chaperons, heat shock proteins (HSPs). Having a favorable safety profile, curcumin can be an alternative therapeutic choice in treating neurodegenerative disorders like HD. This review will focus on mechanistic aspects of curcumin in treating or preventing HD and its potential to arrest disease progression and will open new dimensions for safe and effective therapeutic agents in diminishing HD.

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