Molecular Pathogenesis in Huntington’s Disease

Иллариошкин, С.Н.; Klyushnikov, S. A.; Vigont, Vladimir; Seliverstov, Yury; Kaznacheyeva, Еlena

doi:10.1134/s0006297918090043

Cited by 55 publications

(34 citation statements)

References 85 publications

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“…Huntington disease (HD) is a rare genetic autosomal dominant neurodegenerative syndrome triggered by expanded CAG repeats in the huntingtin gene, which leads to pathological elongation of huntingtin with a polyglutamine tract. The neurodegenerative conditions caused due to HD lead to cognitive, motor, and psychiatric symptoms, atrophy of the basal ganglia and the cerebral cortex (Wright et al, 2017;Illarioshkin et al, 2018). Transcriptional dysregulation has been suggested a prominent mechanism for pathogenesis of HD (Sharma and Taliyan, 2015b).…”

Section: Huntington Diseasementioning

confidence: 99%

Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation

2020

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Histone deacetylases (HADC) are the enzymes that remove acetyl group from lysine residue of histones and non-histone proteins and regulate the process of transcription by binding to transcription factors and regulating fundamental cellular process such as cellular proliferation, differentiation and development. In neurodegenerative diseases, the histone acetylation homeostasis is greatly impaired, shifting towards a state of hypoacetylation. The histone hyperacetylation produced by direct inhibition of HDACs leads to neuroprotective actions. This review attempts to elaborate on role of small molecule inhibitors of HDACs on neuronal differentiation and throws light on the potential of HDAC inhibitors as therapeutic agents for treatment of neurodegenerative diseases. The role of HDACs in neuronal cellular and disease models and their modulation with HDAC inhibitors are also discussed. Significance of these HDAC inhibitors has been reviewed on the process of neuronal differentiation, neurite outgrowth and neuroprotection regarding their potential therapeutic application for treatment of neurodegenerative diseases.

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Section: Huntington Diseasementioning

confidence: 99%

Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation

2020

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“…HTT plays an important role in neuronal transport. The interaction of HTT with dynein and HAP1, proteins that regulate the transport of organelles, have been reported, which, when the complex is disturbed, lead to dysfunction of the axonal transport (for a review see [285,286]).…”

Section: Neuronal Cytoskeleton Abnormalities Generate Neurodegenerationmentioning

confidence: 99%

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Muñoz-Lasso

Romá‐Mateo

Pallardó

et al. 2020

Cells

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Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better understanding of the molecular mechanisms underlying neurological diseases and allow us to see beyond our current knowledge for the development of new treatments. The neuronal cytoskeleton can be described as an organelle formed by the three-dimensional lattice of the three main families of filaments: actin filaments, microtubules, and neurofilaments. This organelle organizes well-defined structures within neurons (cell bodies and axons), which allow their proper development and function through life. Here, we will provide an overview of both the basic and novel concepts related to those cytoskeletal proteins, which are emerging as potential targets in the study of the pathophysiological mechanisms underlying neurological disorders.

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“…The disease remains progressive and incurable as well as finally leads to imminent death approximately 15 years after the diagnosis [97,98]. Characteristic symptoms of HD include involuntary, jerky movements of the limbs named twitching or chorea, as well as dystonia, bradykinesia, myoclonus, dementia, personality changes, and depression [73,99]. The onset of psychiatric and cognitive defects appears earlier than that of motor abnormalities, during early to mid-adult life [98,100].…”

Section: Other Neurodegenerative Diseasesmentioning

confidence: 99%

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

Rozpędek‐Kamińska

Siwecka

Wawrzynkiewicz

et al. 2020

IJMS

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Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism—accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.

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Molecular Pathogenesis in Huntington’s Disease

Cited by 55 publications

References 85 publications

Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation

Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

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