Related Experiment Video

Updated: May 6, 2026

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells
08:53

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells

Published on: May 16, 2017

8.4K

C9orf72-associated FTD/ALS: when less is more

Peter K Todd1, Henry L Paulson

  • 1Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.

Neuron
|October 22, 2013
PubMed

Insights

Hexanucleotide repeat expansions in C9ORF72 are linked to neurodegeneration in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Suppressing the toxic repeat RNA transcript offers a promising therapeutic strategy for these conditions.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Hexanucleotide repeat expansions in the C9ORF72 gene are a known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).
  • The precise molecular mechanisms by which these repeat expansions lead to neurodegeneration remain largely unknown.

Discussion:

  • Donnelly et al. (2013) identified a pathogenic gain-of-function cascade triggered by C9ORF72 repeat expansions.
  • This cascade involves the toxic RNA produced by the expanded repeats.

Key Insights:

  • The study demonstrates that suppressing the expression of the repeat transcript can correct the pathogenic cascade.
  • This finding highlights the critical role of toxic RNA in C9ORF72-associated neurodegeneration.

Outlook:

  • Targeting and eliminating the toxic RNA offers a potential therapeutic avenue for FTD and ALS.
  • Further research into RNA-targeting strategies could lead to novel treatments for these devastating neurological disorders.

More Related Videos

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis08:59

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis

Published on: July 16, 2021

2.5K
Measuring RAN Peptide Toxicity in C. elegans10:49

Measuring RAN Peptide Toxicity in C. elegans

Published on: April 30, 2020

6.0K

Related Concept Videos

Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and...
44
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...
38
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...
166
Alzheimer's Disease: Overview01:26

Alzheimer's Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
1.7K
Amyloid Fibrils03:03

Amyloid 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,...
10.4K
Amyloid Fibrils03:03

Amyloid Fibrils

5.3K