Related Experiment Video
Updated: Jul 11, 2026
08:16
Caenorhabditis elegans as a Model System for Discovering Bioactive Compounds Against Polyglutamine-Mediated Neurotoxicity
Published on: September 21, 2021
Polyglutamine diseases: emerging concepts in pathogenesis and therapy
1Department of Neurology, UCSF, San Francisco, CA 94143, USA.
Human Molecular Genetics
|October 4, 2007
Summary
Polyglutamine diseases stem from expanded CAG repeats, causing toxic protein misfolding. Emerging therapies target cellular disruptions and the pathogenic proteins themselves.
Area of Science:
- Neurodegenerative Diseases
- Molecular Biology
- Genetics
Background:
- Polyglutamine diseases are a class of neurodegenerative disorders.
- These conditions arise from expanded CAG triplet repeats in specific genes.
- Pathogenic proteins with expanded glutamine tracts cause these diseases, including Huntington's disease and spinocerebellar ataxias.
Purpose of the Study:
- To review emerging concepts in the pathogenesis of polyglutamine diseases.
- To discuss current and future therapeutic strategies for these conditions.
Main Methods:
- Review of current scientific literature on polyglutamine diseases.
- Analysis of key pathogenetic mechanisms, including protein misfolding, aggregation, and cellular disturbances.
- Evaluation of therapeutic approaches targeting protein expression, conformation, and cellular perturbations.
Main Results:
- Key pathogenetic factors include proteolytic cleavage, conformational changes, protein aggregation, and transcriptional/metabolic disturbances.
- The role of functional perturbation of target proteins by polyglutamine expansion is a significant consideration.
- Therapeutic strategies focus on mitigating cellular dysfunction and directly targeting the pathogenic polyglutamine proteins.
Conclusions:
- Understanding the complex pathogenesis of polyglutamine diseases is crucial for developing effective treatments.
- Targeting protein misfolding, aggregation, and cellular disruptions offers promising therapeutic avenues.
- Further research into polyglutamine protein expression, cleavage, and conformation is essential for advancing treatment options.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:21Huntington 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,...
01:22Lysosomal Hydrolases
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
01:24Parkinson 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...
01:15Parkinson'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...
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life