ArticleHuman molecular genetics2010
A point mutation in the dynein heavy chain gene leads to striatal atrophy and compromises neurite outgrowth of striatal neurons.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 61 citations in OpenAlex.
- Patient-specific mutation of Dync1h1 in mice causes brain and behavioral deficits.Neurobiology of disease · 2024Article
- Deciphering the distinct transcriptomic and gene regulatory map in adult macaque basal ganglia cells.GigaScience · 2022Article
- Decreased anterograde transport coupled with sustained retrograde transport contributes to reduced axonal mitochondrial density in tauopathy neurons.Frontiers in molecular neuroscience · 2022Article
- Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington's disease.Acta neuropathologica communications · 2020Article
- Article
- IKK2/NF-κB signaling protects neurons after traumatic brain injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Regulation of motor proteins, axonal transport deficits and adult-onset neurodegenerative diseases.Neurobiology of disease · 2017Review
- Sustained Systemic Glucocerebrosidase Inhibition Induces Brain α-Synuclein Aggregation, Microglia and Complement C1q Activation in Mice.Antioxidants & redox signaling · 2015Article
- A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.Cell reports · 2015Article
- Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration.Human molecular genetics · 2015Article
- Mutual exacerbation of peroxisome proliferator-activated receptor γ coactivator 1α deregulation and α-synuclein oligomerization.Annals of neurology · 2015Article
- Alteration of dynein function affects α-synuclein degradation via the autophagosome-lysosome pathway.International journal of molecular sciences · 2013Article
- Cytoplasmic dynein heavy chain: the servant of many masters.Trends in neurosciences · 2013Review
- Dynein mutations associated with hereditary motor neuropathies impair mitochondrial morphology and function with age.Neurobiology of disease · 2013Article
- Mutant Huntingtin alters retrograde transport of TrkB receptors in striatal dendrites.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Diffusion tensor magnetic resonance imaging of the brain in APP transgenic mice: a cohort study.PloS one · 2013Article
- PATHOLOGIES OF AXONAL TRANSPORT IN NEURODEGENERATIVE DISEASES.Translational neuroscience · 2012Article
- A novel phenotype for the dynein heavy chain mutation Loa: altered dendritic morphology, organelle density, and reduced numbers of trigeminal motoneurons.The Journal of comparative neurology · 2012Article
- Huntington's disease and the striatal medium spiny neuron: cell-autonomous and non-cell-autonomous mechanisms of disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2012Review
- Article
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular motor dynein and its associated regulatory subunit dynactin have been implicated in several neurodegenerative conditions of the basal ganglia, such as Huntington's disease (HD) and Perry syndrome, an atypical Parkinson-like disease. This pathogenic role has been largely postulated from the existence of mutations in the dynactin subunit p150(Glued). However, dynactin is also able to act independently of dynein, and there is currently no direct evidence linking dynein to basal ganglia degeneration. To provide such evidence, we used here a mouse strain carrying a point mutation in the dynein heavy chain gene that impairs retrograde axonal transport. These mice exhibited motor and behavioural abnormalities including hindlimb clasping, early muscle weakness, incoordination and hyperactivity. In vivo brain imaging using magnetic resonance imaging showed striatal atrophy and lateral ventricle enlargement. In the striatum, altered dopamine signalling, decreased dopamine D1 and D2 receptor binding in positron emission tomography SCAN and prominent astrocytosis were observed, although there was no neuronal loss either in the striatum or substantia nigra. In vitro, dynein mutant striatal neurons displayed strongly impaired neuritic morphology. Altogether, these findings provide a direct genetic evidence for the requirement of dynein for the morphology and function of striatal neurons. Our study supports a role for dynein dysfunction in the pathogenesis of neurodegenerative disorders of the basal ganglia, such as Perry syndrome and HD.
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