Mutations in Dynein Link Motor Neuron Degeneration to Defects in Retrograde Transport
The Honourable Society of Lincoln's Inn · Queen Mary University of London · +4 more institutions
Abstract
Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Although the causative genetic alterations are known for some cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown. Here we show that missense point mutations in the cytoplasmic dynein heavy chain result in progressive motor neuron degeneration in heterozygous mice, and in homozygotes this is accompanied by the formation of Lewy-like inclusion bodies, thus resembling key features of human pathology. These mutations exclusively perturb neuron-specific functions of…
Citation impact
- FWCI
- 26.52
- Percentile
- 100%
- References
- 29
Authors
39- MHMajid HafezparastCorresponding
The Honourable Society of Lincoln's Inn, Queen Mary University of London, Royal London Hospital, Ingenium (Germany), National Hospital for Neurology and Neurosurgery, University College London
- RKRainer Klocke
The Honourable Society of Lincoln's Inn, Queen Mary University of London, Royal London Hospital, Ingenium (Germany), National Hospital for Neurology and Neurosurgery, University College London
- CRChristiana Ruhrberg
The Honourable Society of Lincoln's Inn, Queen Mary University of London, Royal London Hospital, Ingenium (Germany), National Hospital for Neurology and Neurosurgery, University College London
- AMAndreas Marquardt
The Honourable Society of Lincoln's Inn, Queen Mary University of London, Royal London Hospital, Ingenium (Germany), National Hospital for Neurology and Neurosurgery, University College London
- AAAzlina Ahmad‐Annuar
The Honourable Society of Lincoln's Inn, Queen Mary University of London, Royal London Hospital, Ingenium (Germany), National Hospital for Neurology and Neurosurgery, University College London
Topics & keywords
- Amyotrophic lateral sclerosis
- Spinal muscular atrophy
- Motor neuron
- SMA*
- Biology
- Dynein
- Degeneration (medical)
- Missense mutation
- Good health and well-being