Mutation of Tyrosine Sites in the Human Alpha-Synuclein Gene Induces Neurotoxicity in Transgenic Mice with Soluble Alpha-Synuclein Oligomer Formation.

Overexpression of α-synuclein with tyrosine mutated to phenylalanine at position 125 leads to a severe phenotype with motor impairment and neuropathology in . Here, we hypothesized that tyrosine mutations would similarly lead to impaired motor performance with neuropathology in a rodent model. In transgenic mice (ASO), tyrosines at positions 125, 133, and 136 in human α-synuclein were mutated to phenylalanine and cloned into a Thy1.

A microbial supply chain for production of the anti-cancer drug vinblastine.

Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine. As MIAs are difficult to chemically synthesize, the world's supply chain for vinblastine relies on low-yielding extraction and purification of the precursors vindoline and catharanthine from the plant Catharanthus roseus, which is then followed by simple in vitro chemical coupling and reduction to form vinblastine at an industrial scale. Here, we demonstrate the de novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast, and in vitro chemical coupling to vinblastine.

Guillain-Barré syndrome in Denmark: a population-based study on epidemiology, diagnosis and clinical severity.

Objectives: To describe the epidemiology and clinical heterogeneity of Guillain-Barré syndrome (GBS) in Denmark and to compare a population-based cohort to prospectively included patients in the International GBS Outcome Study (IGOS).

Methods: The incidence rate (IR) of GBS in Denmark from September 2012 to December 2015, applying the National Institute of Neurological Disorders and Stroke (NINDS) diagnostic criteria, was estimated and the level of diagnostic certainty was described with the Brighton criteria. All cases registered with a diagnosis of GBS or other inflammatory neuropathies in the Danish National Hospital Registry were reviewed for diagnostic criteria and for information on treatment and clinical course.

Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation.

Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced cytosolic Ca levels followed by a later Ca increase.