scholarly journals HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in a Drosophila model of Huntington's Disease

2021 ◽  
Author(s):  
Pavitra Prakash ◽  
Arpit Kumar Pradhan ◽  
Vasu Sheeba
Keyword(s):  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Molecular Chaperones ◽  
Therapeutic Implications ◽  
Pigment Dispersing Factor ◽  
Drosophila Model ◽  
First Time ◽  
Circadian Dysfunction

Circadian disturbances are early features of neurodegenerative diseases, including Huntington's Disease (HD), affecting the quality of life of patients and caregivers. Emerging evidence suggests that circadian decline feeds-forward to neurodegenerative symptoms, exacerbating them, highlighting a need for restoring circadian health. Therefore, we asked whether any of the known neurotoxic modifiers can suppress circadian dysfunction. We performed a screen of neurotoxicity-modifier genes to suppress circadian behavioural arrhythmicity in a Drosophila circadian HD model. Notably, the molecular chaperones HSP40 and HSP70 (Heat Shock Protein) emerged as significant suppressors in the circadian context, with HSP40 being the more potent mitigator of HD-induced deficits. Upon HSP40 overexpression in the Drosophila circadian ventrolateral neurons (LNv), the behavioural rhythm rescue was associated with neuronal rescue of loss in circadian proteins from small LNv soma. Specifically, there was a restoration of the molecular clock protein Period and its oscillations in young flies and a long-lasting rescue of the output neuropeptide Pigment Dispersing Factor. Significantly, there was a reduction in the expanded Huntingtin inclusion load, concomitant with the appearance of a spot-like Huntingtin form. Thus, we provide evidence for the first time that implicates the neuroprotective chaperone HSP40 in circadian rehabilitation. Given the importance of proteostasis and circadian health in neurodegenerative diseases, the involvement of molecular chaperones in circadian maintenance has broader therapeutic implications.

scholarly journals Novel Therapeutic Approach to Induce Autophagy in a Drosophila Model for Huntington’s Disease

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 495
Author(s):  
Marta Martinez-Vicente
Keyword(s):  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Therapeutic Approach ◽  
Autophagy Induction ◽  
Drosophila Model ◽  
Novel Therapeutic

Autophagy induction is an attractive therapeutic approach to ameliorate aggregate accumulation in many neurodegenerative diseases [...]

scholarly journals Modulating glial genes involved in synaptic function mitigates pathogenesis and behavioral deficits in a Drosophila model of Huntington’s Disease

2020 ◽  
Author(s):  
Tarik S. Onur ◽  
Andrew Laitman ◽  
He Zhao ◽  
Ryan Keyho ◽  
Hyemin Kim ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
High Throughput ◽  
Synaptic Function ◽  
Behavioral Deficits ◽  
Drosophila Model ◽  
Conserved Genes ◽  
Transcriptomic Changes ◽  
The Brain

AbstractMost research on neurodegenerative diseases has focused on neurons, yet glia help form and maintain the synapses whose loss is so prominent in these conditions. To investigate the contributions of glia to Huntington’s disease (HD), we studied transcriptomic changes in HD human, HD mice, and Drosophila expressing human mutant Huntingtin (mHTT) in either glia, neurons or both. A large portion of conserved genes are concordantly dysregulated across the three species; we tested these genes in a high-throughput behavioral assay and found that downregulation of genes involved in synapse assembly mitigated pathogenesis and behavioral deficits. To our surprise, mitigating glial pathogenesis by dNRXN3 knockdown was sufficient to improve the phenotype of flies expressing mHTT in neurons, suggesting that mHTT’s toxic effects in glia ramify throughout the brain. This supports a model in which dampening synaptic function is protective because it attenuates the excitotoxicity that characterizes HD.

scholarly journals Management of Traumatic Ulcerations of Lips in a Case of Huntington’s Disease: A Novel Application of Essix Retainer

2021 ◽  
pp. 030157422110234
Author(s):  
Mohamed Iqbal J
Keyword(s):  
Quality Of Life ◽  
Characteristic Feature ◽  
Neurodegenerative Disease ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Complete Resolution ◽  
Psychiatric Symptoms

Huntington’s disease is a progressive neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. Dystonia of muscles is a characteristic feature of this condition. A case of Huntington’s disease, with orofacial dystonia, leading to severe uncontrolled biting of the lips, was referred by the Department of Neurology. Deep traumatic ulcerations were found in both upper and lower lips. A simple Essix retainer was fabricated and inserted, which acted as a barrier for the teeth from injuring the lips. The ulcers showed complete resolution in 3 to 4 weeks. The vacuum-formed retainers resulted in a good fit and resisted removal by the uncontrolled contortions of the orofacial muscles. The Essix retainer can be effectively used in improving the quality of life of patients, with Huntington’s disease, having such dystonia-related injuries to lips.

scholarly journals Psychometric Properties and Validation of the Polish Version of the 12-Item World Health Organization Disability Assessment Schedule 2.0 in Patients with Huntington’s Disease

2021 ◽  
Vol 10 (5) ◽  
pp. 1053
Author(s):  
Agnieszka Ćwirlej-Sozańska ◽  
Bernard Sozański ◽  
Mateusz Kupczyk ◽  
Justyna Leszczak ◽  
Andrzej Kwolek ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Huntington's Disease ◽  
Psychometric Properties ◽  
Huntington’S Disease ◽  
Scale Score ◽  
World Health ◽  
Disability Assessment ◽  
Whodas 2.0 ◽  
Score Reliability

Background: Huntington’s disease is a progressive neurodegenerative disorder that usually manifests in adulthood and is inherited in an autosomal dominant manner. The main aim of the study was to assess the psychometric properties of the 12-item WHO Disability Assessment Schedule (WHODAS) 2.0 in studying the level of disability in people with Huntington’s disease. Method: This is a cross-sectional study that covered 128 people with Huntington’s disease living in Poland. We examined scale score reliability, internal consistency, convergent validity, and known-group validity. The disability and quality of life of people with Huntington’s disease were also assessed. Results: The scale score reliability of the entire tool for the research group was high. The Cronbach’s α test result for the whole scale was 0.97. Cronbach’s α for individual domains ranged from 0.95 to 0.79. Time consistency for the overall result was 0.99 and for particular domains ranged from 0.91 to 0.99, which confirmed that the scale was consistent over time. All of the 12-item WHODAS 2.0 domains negatively correlated with all of the Huntington Quality of Life Instrument (H-QoL-I) domains. All correlation coefficients were statistically significant at the level of p < 0.001. The results obtained in the linear regression model showed that with each subsequent point of decrease in BMI the level of disability increases by an average of 0.83 points on the 12-item WHODAS 2.0 scale. With each subsequent year of the disease, the level of disability increases by an average of 1.39 points. Conclusions: This is the first study assessing disability by means of the WHODAS 2.0 in the HD patient population in Poland, and it is also one of the few studies evaluating the validity of the WHODAS 2.0 scale in assessing the disability of people with HD in accordance with the recommendations of DSM-5 (R). We have confirmed that the 12-item WHODAS 2.0 is an effective tool for assessing disability and changes in functioning among people with Huntington’s disease.

Validation of the first quality-of-life measurement for patients with Huntington’s disease

2012 ◽  
Vol 27 (4) ◽  
pp. 208-214 ◽  
Author(s):  
Emilie Clay ◽  
Annunziata De Nicola ◽  
Julie Dorey ◽  
Ferdinando Squitieri ◽  
Samuel Aballéa ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Life Measurement ◽  
Quality Of Life Measurement

scholarly journals Co-Design of Social Impact Domains with the Huntington’s Disease Community

Disabilities ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 116-131
Author(s):  
Natasha Layton ◽  
Natasha Brusco ◽  
Tammy Gardner ◽  
Libby Callaway
Keyword(s):  
Quality Of Life ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Design Process ◽  
Social Life ◽  
Social Inclusion ◽  
Social Impact ◽  
Service Providers ◽  
The Social

Background: For people living with or affected by Huntington’s Disease (HD) to experience a good quality of life, tailored support is required to meet physical, cognitive-behavioral, psychological, and social support needs. Substantial service and knowledge gaps regarding HD exist across support providers and service systems. Measuring unmet needs and what quality of life looks like is a fundamental step required to determine the social impact of service investment and provision. The objectives of this study were to validate and map a draft set of HD Social Impact Domains (HD-SID) against existing national and international outcome frameworks; and evaluate and finalize the HD-SID set using a co-design approach with people with lived experience of, and expertise in, HD. Methods: This research used a qualitative co-design process, with 39 participants across four stakeholder groups (people who were HD gene-positive, gene-negative family members, academics, peak organizations, and service providers) to: (i) map and verify the social life areas impacted by HD; (ii) undertake a rigorous three-phased, qualitative process to critically evaluate the draft HD-SID; and (iii) seek feedback on and endorsement of the HD-SID through this co-design process, with a final set of HD-SID identified. Results: Endorsed HD-SID comprised risks and safety (including housing stability, and economic sustainability) and social inclusion (including health and symptom management, physical wellbeing, emotional wellbeing, and building resilient relationships). Conclusions: Effective measurement of the impacts and outcomes for people with HD is informed by both extant measures and an understanding of the specific population needs. This qualitative co-design research demonstrates that HD-SID resonate with the HD community.

Health-related quality of life in Huntington's disease: A comparison of two generic instruments, SF-36 and SIP

2004 ◽  
Vol 19 (11) ◽  
pp. 1341-1348 ◽  
Author(s):  
Aileen K. Ho ◽  
Anna O.G. Robbins ◽  
Stephen J. Walters ◽  
Stephen Kaptoge ◽  
Barbara J. Sahakian ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Health Related Quality ◽  
Sf 36 ◽  
Related Quality ◽  
Health Related
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