Subject collection: Neurodegenerative Disorders
- A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition
Editors' choice: In vivo validation of a potent DYRK1A inhibitor, with proven clinical safety, using Down-syndrome- and Alzheimer's-disease-like models.
- MicroRNA screening identifies a link between NOVA1 expression and a low level of IKAP in familial dysautonomia
Summary: A miRNA screening conducted in olfactory stem cells from patients links the neuron-specific splicing factor NOVA1 to neurodegeneration in familial dysautonomia.
- A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease
Summary: This work describes the generation of a novel immortalized glucocerebrosidase-deficient neuronal cell model with utility for pathophysiology research and therapeutic development in Gaucher disease.
- Two different pathogenic mechanisms, dying-back axonal neuropathy and pancreatic senescence, are present in the YG8R mouse model of Friedreich’s ataxia
Summary: Frataxin deficiency induces different pathogenic mechanisms in the nervous system and pancreas in a YG8R mouse model of Friedreich's ataxia (FRDA). Thus, the degenerative process in FRDA is determined by the cell type.
- A novel Drosophila model of TDP-43 proteinopathies: N-terminal sequences combined with the Q/N domain induce protein functional loss and locomotion defects
Summary: An engineered TDP-43 construct can be used to induce TDP-43 aggregation in Drosophila, providing a model that could be useful for characterization of pathogenetic mechanisms and drug screening.
- Spontaneous shaker rat mutant – a new model for X-linked tremor/ataxia
Summary: The shaker rat mutant: a new model for essential tremors and ataxia characterized by Purkinje cell degeneration.
- Neurodegeneration in a Drosophila model of adrenoleukodystrophy: the roles of the Bubblegum and Double bubble acyl-CoA synthetases
Drosophila Collection: A new Drosophila model of ALD reveals dysregulation of fatty acid metabolism as causal of neurodegenerative pathologies and has led to the identification of a new candidate gene for ALD in humans.
- Decreased N-TAF1 expression in X-linked dystonia-parkinsonism patient-specific neural stem cells
Summary: This study describes a new iPSC model of X-linked dystonia-parkinsonism (XDP), which was initially validated by demonstrating a similar transcriptional defect as has been previously reported in XDP brain tissue.
- 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.