Subject collection: Neurodegenerative Disorders
- Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function
Drosophila Collection: Loss of sws in glia results in locomotion deficits, suggesting that glial changes contribute to the paralysis and spastic paraplegia in humans carrying mutations in its orthologue, NTE.
- The calcineurin inhibitor Sarah (Nebula) exacerbates Aβ42 phenotypes in a Drosophila model of Alzheimer's disease
Drosophila Collection: Chronically increased levels of Sarah (Nebula), a calcineurin inhibitor, cause mitochondria dysfunction and subsequently increased Aβ42-induced cytotoxicity in Drosophila.
- Tau excess impairs mitosis and kinesin-5 function, leading to aneuploidy and cell death
Drosophila Collection: We show that Tau, a microtubule-binding protein involved in many neurodegenerative diseases, impairs mitosis when in excess. We show that this occurs via the inhibition of the kinesin-5 mitotic motor.
- Assessing a peptidylic inhibitor-based therapeutic approach that simultaneously suppresses polyglutamine RNA- and protein-mediated toxicities in patient cells and Drosophila
Drosophila Collection: We identified a novel peptidylic inhibitor against expanded CAG RNA toxicity. Our study highlights the importance of simultaneously targeting both toxic RNA and protein species in treating polyQ degeneration.
- X-linked Christianson syndrome: heterozygous female Slc9a6 knockout mice develop mosaic neuropathological changes and related behavioral abnormalities
Editors' choice: Slc9a6 knockout mice are a model of the X-linked neurodevelopmental and neurological disorder, Christianson syndrome. We show that heterozygous female mice express mosaic changes comparable to neuropathological abnormalities identified in mutant males.
- The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders
Summary: Labrador retrievers with hereditary copper toxicosis are a useful new model for copper-metabolism disorders.
- Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy
Summary: This study provides the first evidence in human models of spinal muscular atrophy of impaired mitochondrial dynamics, which serve as potential therapeutic targets for this devastating disease.
- Huntington disease iPSCs show early molecular changes in intracellular signaling, the expression of oxidative stress proteins and the p53 pathway
Summary: This research demonstrates that dysregulation of signaling pathways is a very early event in the pathogenesis of Huntington disease and that these pathways are already dysregulated in cells at the stage of pluripotency.
- Sun1 deficiency leads to cerebellar ataxia in mice
Summary: Mice lacking Sun proteins serve as a working model to study SYNE1-associated cerebellar ataxia; they will also be useful in identifying therapeutic targets for neurodegenerative diseases involving Purkinje cell loss.
- A natural human IgM that binds to gangliosides is therapeutic in murine models of amyotrophic lateral sclerosis
Summary: A single peripheral dose of a recombinant natural human IgM increases lifespan and delays neurological deficits in mouse models of human ALS.