A convenient model of serum-induced reactivity of human astrocytes to investigate astrocyte-derived extracellular vesicles.

Extracellular vesicles (EVs) are secreted by all cells in the CNS, including neurons and astrocytes. EVs are lipid membrane enclosed particles loaded with various bioactive cargoes reflecting the dynamic activities of cells of origin. In contrast to neurons, the specific role of EVs released by astrocytes is less well understood, partly due to the difficulty in maintaining primary astrocyte cultures in a quiescent state.

CDK12 inhibition reduces abnormalities in cells from patients with myotonic dystrophy and in a mouse model.

Myotonic dystrophy type 1 (DM1) is an RNA-based disease with no current treatment. It is caused by a transcribed CTG repeat expansion within the 3' untranslated region of the dystrophia myotonica protein kinase () gene. Mutant repeat expansion transcripts remain in the nuclei of patients' cells, forming distinct microscopically detectable foci that contribute substantially to the pathophysiology of the condition.

Dynamic metabolic patterns tracking neurodegeneration and gliosis following 26S proteasome dysfunction in mouse forebrain neurons.

Metabolite profiling is an important tool that may better capture the multiple features of neurodegeneration. With the considerable parallels between mouse and human metabolism, the use of metabolomics in mouse models with neurodegenerative pathology provides mechanistic insight and ready translation into aspects of human disease. Using 400 MHz nuclear magnetic resonance spectroscopy we have carried out a temporal region-specific investigation of the metabolome of neuron-specific 26S proteasome knockout mice characterised by progressive neurodegeneration and Lewy-like inclusion formation in the forebrain.

NAD-biosynthetic enzyme NMNAT1 reduces early behavioral impairment in the htau mouse model of tauopathy.

NAD metabolism and the NAD biosynthetic enzymes nicotinamide nucleotide adenylyltransferases (NMNATs) are thought to play a key neuroprotective role in tauopathies, including Alzheimer's disease. Here, we investigated whether modulating the expression of the NMNAT nuclear isoform NMNAT1, which is important for neuronal maintenance, influences the development of behavioral and neuropathological abnormalities in htau mice, which express non-mutant human tau isoforms and represent a model of tauopathy relevant to Alzheimer's disease. Prior to the development of cognitive symptoms, htau mice exhibit tau hyperphosphorylation associated with a selective deficit in food burrowing, a behavior reminiscent to activities of daily living which are impaired early in Alzheimer's disease.

A novel role for the immunophilin FKBP52 in motor coordination.

FKBP52 is a ubiquitously distributed immunophilin that has been associated with wide-ranging functions in cell signalling as well as hormonal and stress responses. Amongst other pathways, it acts via complex-formation with corticosteroid receptors and has consequently been associated with stress- and age- related neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Reduced levels of FKBP52 have been linked to tau dysfunction and amyloid beta toxicity in AD.