Subject collection: Neurodegenerative Disorders
- Inducible expression of human C9ORF72 36× G4C2 hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice
Summary: Only 36 C9ORF72 repeats are sufficient for RAN translation in a new mouse model for amyotrophic lateral sclerosis and frontotemporal dementia. Reducing toxic dipeptides can prevent but not reverse the phenotype.
- TDP-43 mislocalization drives neurofilament changes in a novel model of TDP-43 proteinopathy
Summary: We examined the cellular effects of mislocalization of TDP-43, a key pathological protein in amyotrophic lateral sclerosis and frontotemporal dementia, using the eye as a model and demonstrated axonal cytoskeleton alterations.
- Mistargeting of secretory cargo in retromer-deficient cells
Summary: Using Drosophila larval salivary glands as a model system, we show a new role for retromer in trafficking of secretory membrane and cargo proteins during regulated exocytosis, which could be relevant in neurodegenerative diseases.
- Restoration of motor learning in a mouse model of Rett syndrome following long-term treatment with a novel small-molecule activator of TrkB
Editor's choice: Long-term intermittent treatment with a newly developed partial agonist of the TrkB neurotrophin receptor reverses deficits in motor learning and respiration in a mouse model of Rett syndrome.
- Modeling neurodegeneration in Caenorhabditis elegans
Summary: While unsurpassed as an experimental system for fundamental biology, Caenorhabditis elegans remains undervalued for its translational potential. Here, we highlight significant outcomes from, and resources available for, C. elegans-based research into neurodegenerative disorders.
- Machine learning discriminates a movement disorder in a zebrafish model of Parkinson's disease
Summary: Using computational analyses to harness artificial intelligence, we have tested a genetic model of Parkinson's disease and reveal a distinct movement phenotype in adult zebrafish lacking Dj-1.
- CHIP mutations affect the heat shock response differently in human fibroblasts and iPSC-derived neurons
Summary: Cell viability, expression and immunocytochemical analyses reveal that mutations in STUB1 that cause SCAR16 impair the heat-shock response in patient-derived fibroblasts, but not in iPSC-derived cortical neurons.
- Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders
Summary: The APOE ε4 allele and female sex are among the strongest risk factors for late-onset Alzheimer's disease. We explore how the interplay between these factors affects risk for this and other age-related neurodegenerative diseases.
- Early evidence of delayed oligodendrocyte maturation in the mouse model of mucolipidosis type IV
Summary: We show that loss of the lysosomal channel TRPML1, responsible for mucolipidosis IV, leads to delayed maturation of oligodendrocytes in early postnatal development, resulting in brain hypomyelination.
- Mitochondrial damage and senescence phenotype of cells derived from a novel frataxin G127V point mutation mouse model of Friedreich's ataxia
Summary: Sole expression of the mutant frataxin G127V protein is sufficient for viability of the first Friedreich's ataxia point mutation mouse model, but induces premature senescence in isolated cells.