Subject collection: Neurodegenerative Disorders
- Effects of subthalamic deep brain stimulation on striatal metabolic connectivity in a rat hemiparkinsonian model
Summary: Deep brain stimulation in the subthalamic nucleus in rats with a unilateral dopaminergic lesion established a new functional interhemispheric striatal network.
- Inhibition of the IGF-1–PI3K–Akt–mTORC2 pathway in lipid rafts increases neuronal vulnerability in a genetic lysosomal glycosphingolipidosis
Summary: The authors present a mechanistic model to understand how alterations of the membrane architecture by the progressive accumulation of sphingolipids undermines basic cell function, with potential implications for a variety of genetic sphingolipidoses and adult neurodegenerative conditions.
- Amyotrophic lateral sclerosis mutant TDP-43 may cause synaptic dysfunction through altered dendritic spine function
Summary: Loss of synaptic GluR1, and reduced excitability within pyramidal neurons, implicates hypoexcitability and attenuated synaptic function in the pathogenic decline of neuronal function in TDP-43-associated ALS.
- Recapitulating Parkinson's disease pathology in a three-dimensional human neural cell culture model
Editor's choice: This study describes a novel 3D cell culture model that recapitulates key features of neuropathology in synucleinopathies, including large, nuclear-associated α-synuclein and ubiquitin-positive inclusions.
- VPS13A is closely associated with mitochondria and is required for efficient lysosomal degradation
Summary: VPS13A, which is implicated in chorea-acanthocytosis, is essential for efficient lysosomal degradation, while localized in close association with mitochondria. We propose that inter-organelle communication may be relevant in the pathogenesis of the disease.
- ApoE-associated modulation of neuroprotection from Aβ-mediated neurodegeneration in transgenic Caenorhabditis elegans
Summary: We report new humanized nematode models of amyloid-beta and apolipoprotein E gene expression, examining readouts for neurodegeneration, behavior, cellular function and survival, to elucidate the relative contributions of the proteins to the underlying pathology of Alzheimer's disease.
- SOD1 activity threshold and TOR signalling modulate VAP(P58S) aggregation via reactive oxygen species-induced proteasomal degradation in a Drosophila model of amyotrophic lateral sclerosis
Summary: ALS8/VAPB(P58S) aggregates appear to be cleared by an increase in cellular reactive oxygen species, which, in turn, triggers proteasomal degradation.
- Yeast-model-based study identified myosin- and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis
Summary: Using the vps13Δ strain, a yeast model of the neurodegenerative disorder chorea-acanthocytosis, we found that its defects can be overcome by reduction of calcineurin activity and/or type-I-myosin activation.
- SUMOylation by SUMO2 is implicated in the degradation of misfolded ataxin-7 via RNF4 in SCA7 models
Summary: In spinocerebellar ataxia type 7, SUMOylation contributes to the clearance of mutant ATXN7. SUMO2-modified ATXN7 interacts with the SUMO-dependent ubiquitin ligase RNF4, which polyubiquitinates ATXN7, promoting its proteasomal degradation.
- A transgenic minipig model of Huntington's disease shows early signs of behavioral and molecular pathologies
Summary: Here, we show that a minipig model of Huntington's disease mimics human neurodegeneration and holds promise for future intervention studies. However, minipig peripheral blood mononuclear cells express no detectable mutant huntingtin, eliminating their use as monitoring tools.