scholarly journals The Role of Autophagy and Mitophagy in Huntington’s Disease

2021 ◽  
Vol 16 ◽  
pp. 1-10
Author(s):  
Akhila Eswaran ◽  
Crystale Siew Ying Lim ◽  
Soi Moi Chye ◽  
Anna Pick Kiong Ling ◽  
Rhun Yian Koh
Keyword(s):  
Mitochondrial Dysfunction ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Autosomal Dominant ◽  
Neurodegenerative Disorder ◽  
Motor Functions ◽  
Cellular Changes ◽  
Psychiatric Disturbances ◽  
Polyglutamine Expansions

Huntington’s disease (HD) is an inherited autosomal-dominant neurodegenerative disorder that occurs due to mutations in the polyglutamine expansions of the Huntingtin protein (Htt). HD is characterised by the loss of cognitive and motor functions, as well as the development of emotional and psychiatric disturbances. The HD pathology is manifested through the cellular changes that arise due to the toxic functions of mutant Htt (mHtt). Autophagy is a lysosomal pathway that functions to remove damaged intracellular components while mitophagy is a selective form of autophagy involving mitochondria; and PINK1/Parkin-mediated mitophagy is the most well-understood pathway. Mitochondrial dysfunction and defects in mitophagy can be linked to the pathogenesis of HD. Previous research has shown that the presence of mHtt hinders mitophagy; while PINK1/Parkin-mediated mitophagy provides neuroprotection in HD. Hence, this review discusses the roles and regulations of mitophagy, along with an overview of mitophagy in HD.

scholarly journals Non-Cell Autonomous and Epigenetic Mechanisms of Huntington’s Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12499
Author(s):  
Chaebin Kim ◽  
Ali Yousefian-Jazi ◽  
Seung-Hye Choi ◽  
Inyoung Chang ◽  
Junghee Lee ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Trinucleotide Repeat ◽  
Neurodegenerative Disorder ◽  
Involuntary Movement ◽  
Therapeutic Approaches ◽  
Exon 1 ◽  
Human Chromosome 4 ◽  
The Brain

Huntington’s disease (HD) is a rare neurodegenerative disorder caused by an expansion of CAG trinucleotide repeat located in the exon 1 of Huntingtin (HTT) gene in human chromosome 4. The HTT protein is ubiquitously expressed in the brain. Specifically, mutant HTT (mHTT) protein-mediated toxicity leads to a dramatic degeneration of the striatum among many regions of the brain. HD symptoms exhibit a major involuntary movement followed by cognitive and psychiatric dysfunctions. In this review, we address the conventional role of wild type HTT (wtHTT) and how mHTT protein disrupts the function of medium spiny neurons (MSNs). We also discuss how mHTT modulates epigenetic modifications and transcriptional pathways in MSNs. In addition, we define how non-cell autonomous pathways lead to damage and death of MSNs under HD pathological conditions. Lastly, we overview therapeutic approaches for HD. Together, understanding of precise neuropathological mechanisms of HD may improve therapeutic approaches to treat the onset and progression of HD.

scholarly journals The Role of the Caudate in Nonmotor Behaviors in Huntington’s Disease

1992 ◽  
Vol 5 (4) ◽  
pp. 205-214 ◽  
Author(s):  
D. H. Jacobs ◽  
S. J. Huber
Keyword(s):  
Executive Function ◽  
Basal Ganglia ◽  
Huntington's Disease ◽  
Caudate Nucleus ◽  
Huntington’S Disease ◽  
Limbic Structures ◽  
Psychiatric Disturbances ◽  
Behavioral Impairments

Neuropsychologic data suggest an important role for the caudate nucleus (CN) in behavioral impairments in Huntington's disease (HD). These include abnormalities in executive function, egocentric visuospatial representations, communication, and retrieval of declarative memories, changes in personality, and psychiatric disturbances. Animal paradigms of CN lesions support a role for the CN in some of these behaviors. Current theories of basal ganglia function add explanatory value to the role of the CN in these behaviors. A disconnection of the caudate from limbic structures, including the amygdala may account for many nonmotor behaviors observed in HD.

scholarly journals Implications of the Orb2 Amyloid Structure in Huntington’s Disease

2020 ◽  
Vol 21 (18) ◽  
pp. 6910
Author(s):  
Rubén Hervás ◽  
Alexey G. Murzin ◽  
Kausik Si
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Autosomal Dominant ◽  
Neurodegenerative Disorder ◽  
Structural Data ◽  
Cag Repeat ◽  
Functional Amyloid ◽  
Drosophila Brain ◽  
Structural Insight ◽  
The Brain

Huntington’s disease is a progressive, autosomal dominant, neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. As a result, the translated protein, huntingtin, contains an abnormally long polyglutamine stretch that makes it prone to misfold and aggregating. Aggregation of huntingtin is believed to be the cause of Huntington’s disease. However, understanding on how, and why, huntingtin aggregates are deleterious has been hampered by lack of enough relevant structural data. In this review, we discuss our recent findings on a glutamine-based functional amyloid isolated from Drosophila brain and how this information provides plausible structural insight on the structure of huntingtin deposits in the brain.

scholarly journals Predicting Prognosis of Psychosis in Huntington’s Disease: Case Report and Review of Literature

2017 ◽  
Vol 08 (03) ◽  
pp. 469-471
Author(s):  
Sujita Kumar Kar ◽  
Mohit Kumar Shahi ◽  
Adarsh Tripathi ◽  
Praveen Kumar Sharma
Keyword(s):  
Case Report ◽  
Anxiety Disorders ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Autosomal Dominant ◽  
Neurodegenerative Disorder ◽  
Review Of Literature ◽  
Psychiatric Comorbidities ◽  
Disease Case ◽  
Cognitive Disturbances

ABSTRACTHuntington’s disease (HD) is rare variant of progressive neurodegenerative disorder which follows an autosomal dominant pattern. Psychiatric comorbidities are not uncommon with HD. Mood disorder, cognitive disturbances, anxiety disorders, and psychosis are the psychiatric comorbidities reported with HD. We report here a case of HD, where psychosis developed during illness. Prognosis of psychosis in HD is emphasized in this report with review of literature.

Transcriptional dysregulation in Huntington’s Disease. The role in pathogenesis and potency for pharmacological targeting.

2020 ◽  
Vol 27 ◽  
Author(s):  
Aleksandra Pogoda ◽  
Natalia Chmielewska ◽  
Piotr Maciejak ◽  
Janusz Szyndler
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Regulatory Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Manipulation

: Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the gene that encodes a critical cell regulatory protein, huntingtin (Htt). The expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats causes improper folding of functional proteins and is an initial trigger of pathological changes in the brain. Recent research has indicated that the functional dysregulation of many transcription factors underlies the neurodegenerative processes that accompany HD. These disturbances are caused not only by the loss of wild-type Htt (WT Htt) function but also by the occurrence of abnormalities that result from the action of mutant Htt (mHtt). In this review, we aim to describe the role of transcription factors that are currently thought to be strongly associated with HD pathogenesis, namely, RE1-silencing transcription factor, also known as neuron-restrictive silencer factor (REST/NRSF), forkhead box proteins (FOXPs), peroxisome proliferator-activated receptor gamma coactivator-1a (PGC1α), heat shock transcription factor 1 (HSF1), and nuclear factor κ light-chain-enhancer of activated B cells (NF-κB). We also take into account the role of these factors in the phenotype of HD as well as potential pharmacological interventions targeting the analyzed proteins. Furthermore, we considered whether molecular manipulation resulting in changes in transcription factor function may have clinical potency for treating HD.

scholarly journals Huntington's Disease with Retinitis Pigmentosa- a Case Report

2017 ◽  
Vol 12 (1) ◽  
pp. 50-52
Author(s):  
Reaz Mahmud ◽  
Mansur Habib
Keyword(s):  
Case Report ◽  
Retinitis Pigmentosa ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Autosomal Dominant ◽  
Neurodegenerative Disorder ◽  
Genetic Mutation ◽  
Medical Documentation ◽  
Dominant Inheritance ◽  
Nucleotide Triplet

Huntington's disease (HD) is a chronic neurodegenerative disorder, characterized by the following triad of clinical hallmarks: autosomal dominant inheritance, choreoathetosis, and dementia. In 1993 the genetic mutation responsible for HD was identified and mapped on the chromosome 4p16.3. The mutation is a characteristic expansion of a CAG nucleotide triplet. In this paper we present a 36-years-old male patient with HD. Additionally he also had retinitis pigmentosa. His pedigree was reconstructed using available medical documentation and tracing other members of his family.Faridpur Med. Coll. J. Jan 2017;12(1): 50-52

Sign in / Sign up

Export Citation Format

Share Document