Neurological disorers

Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders. Binda, C. et al. Nature Struct. Biol. 26 November 2001. (10.1038/nsb732)

Monoamine oxidase B (MAO-B) hydrolyses catecholamines and is a common target of drugs for Parkinson's disease and depression. The authors solved the structure of MAO-B, determined the properties of its active site, and identified the residues involved in substrate recognition. Knowledge of this structure will lead to insights into the catalytic mechanism of MAO-B, explain the differences between MAO-B and MAO-A, and guide the development of MAO-B-specific drugs.

Neurological disorders

Endogenous β-amyloid production in presenilin-deficient embryonic mouse fibroblasts. Armogida, M. et al. Nature Cell Biol. 3, 1030–1033 (2001) [PubMed]

Recent findings have questioned the idea that the presenilins are responsible for γ-secretase activity and the concomitant production of β-amyloid peptides in Alzheimer's disease. This paper contributes to this debate by showing that fibroblasts that lack presenilins produce Aβ40 and Aβ42. By contrast, processing of the Notch protein, which also depends on γ-secretase activity, was abolished in these cells. These findings point to the existence of additional γ-secretases that are distinct from the presenilins.

Development

The Drosophila neuregulin Vein maintains glial survival during axon guidance in the CNS. Hidalgo, A. et al. Dev. Cell 1, 679–690 (2001) [PubMed]

Glial cells contribute to axonal pathfinding by providing guidance cues and trophic support. This paper shows that the relationship is reciprocal: Drosophila neurons promote glial survival by expressing a protein called Vein. Vein shows homology to neuregulin, a molecule known to promote glial survival in vertebrates. The authors provide evidence that Vein expression prevents glial apoptosis, and that loss of Vein function induces glial cell death.

Synaptic plasticity

Remodeling of synaptic actin induced by photoconductive stimulation. Colicos, M. A. et al. Cell 107, 605–616 (2001) [Article]

This paper provides compelling evidence that neuronal activity is accompanied by structural changes at the synapse. To limit the invasiveness of common experimental manipulations, the authors used photoconductive neuronal stimulation. Cells are cultured on a silicon chip and light is applied to single neurons. As the conductivity of silicon changes in response to light, it is possible to pair local illumination with subthreshold electrical stimulation of the whole culture, and detect changes solely in the illuminated neuron. This approach allowed the authors to show that pre- and postsynaptic actin reorganizes transiently in response to a train of stimuli, whereas repeated trains lead to stable actin redistribution and the formation of new synapses.