Related Experiment Video

Updated: Jun 10, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

Huntington's disease

Emmanuel Roze1, Cecilia Bonnet, Sandrine Betuing

  • 1UMRS 952, INSERM, UMR 7224-CNRS Université Pierre et Marie Curie-Paris-6, Paris, France. emmanuel.roze@psl.aphp.fr

Advances in Experimental Medicine and Biology
|August 7, 2010
PubMed

Insights

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Current treatments cannot prevent or slow HD progression, leading to neuronal death and diagnosis-related mortality within 20 years.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Huntington's disease (HD) is a prevalent neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms.
  • It is an autosomal-dominant condition resulting from an unstable expansion of a CAG repeat within the huntingtin gene (IT15).
  • The precise pathophysiology of HD remains incompletely understood, particularly the selective vulnerability of the striatum to mutated huntingtin protein (Htt).

Purpose of the Study:

  • To elucidate the underlying mechanisms contributing to neuronal dysfunction and death in Huntington's disease.
  • To investigate the molecular and cellular processes affected by mutated huntingtin protein (Htt) in the striatum.
  • To provide a comprehensive overview of the current understanding of HD pathophysiology.

Main Methods:

  • Review of existing literature on Huntington's disease genetics and molecular pathology.
  • Analysis of studies investigating the expression and aggregation of mutated huntingtin protein (Htt).
  • Examination of research on cellular processes affected in HD, including transcriptional regulation, energy metabolism, excitotoxicity, axonal transport, and synaptic transmission.

Main Results:

  • Mutated huntingtin protein (Htt) aggregates and disrupts multiple cellular functions.
  • Specific vulnerability of the striatum to mutated Htt, despite widespread expression.
  • Key pathological pathways include transcriptional dysregulation, impaired energy metabolism, excitotoxicity, disrupted axonal transport, and altered synaptic function.

Conclusions:

  • The complex pathophysiology of Huntington's disease involves the convergence of several detrimental cellular events triggered by mutated huntingtin protein (Htt).
  • Neuronal dysfunction and eventual death in HD result from a cascade of molecular and cellular impairments, particularly affecting the striatum.
  • There are currently no available treatments to prevent or slow the progression of Huntington's disease, highlighting the urgent need for therapeutic strategies.

More Related Videos

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System10:52

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System

Published on: December 10, 2021

Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease09:06

Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease

Published on: June 9, 2018

Related Concept Videos

Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
Parkinson's Disease: Overview01:15

Parkinson's Disease: Overview

Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is to...
Parkinson Disease l: Introduction01:24

Parkinson Disease l: Introduction

Parkinson’s disease is a chronic, progressive neurodegenerative disorder that primarily affects movement. It is characterized by motor symptoms such as resting tremors, muscle rigidity, bradykinesia (slowness of movement), and postural instability. Patients may notice hand tremors at rest, stiffness during movement, or a shuffling gait. In addition to motor features, non-motor symptoms include sleep disturbances, mood and behavioral changes, constipation, and cognitive impairment, all of which...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
Disorders of the Nervous Tissue01:28

Disorders of the Nervous Tissue

Nervous tissue is a vital component of the human body's communication system, enabling us to perceive and respond to stimuli. However, like all other tissues, it is vulnerable to disorders and diseases that can significantly impact our neurological functioning.
Homeostatic Imbalances:
Alzheimer's disease manifests as a gradual decline in memory and cognitive abilities, attributed to the buildup of amyloid plaques and neurofibrillary tangles in the brain.
Parkinson's disease arises from the...