Neurodegenerative Disease

BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Ohno, M. et al. Neuron 41, 27–33 (2004).

BACE1 has been identified as one of two key proteases that cleave the amyloid precursor protein to generate the Aβ peptide thought to be central to the pathogenesis of Alzheimer's disease (AD). The development of BACE1 inhibitors as potential therapeutics for AD is supported by this study, which provides the first demonstration that BACE1 gene deletion can rescue memory deficits in an AD animal model by lowering brain Aβ levels.

Structural Genomics

Rapid refinement of crystallographic protein construct definition employing enhanced hydrogen/deuterium exchange MS. Pantazatos, D. et al. Proc. Natl Acad. Sci. USA 101, 751–756 (2004).

Unstructured regions of proteins are an important factor in the frequent failure of efforts to produce protein crystals suitable for structure determination by X-ray crystallography. Removing these regions can help address this issue. Pantazatos et al. describe the application of a general approach to identify these unstructured regions, and show that it can aid the high-throughput production of derivatives of poorly crystallizing proteins that show greatly improved crystallization.

Cardiovascular Disease

A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. Stone, G. W. et al. N. Engl. J. Med. 350, 221–231 (2004).

Implantation of coronary stents is commonly used to relieve an obstruction due to atherosclerosis, but restenosis — re-narrowing at the site at which treatment was performed — still occurs in a significant number of patients, often necessitating repeated revascularization procedures. As a key cause of such restenosis is the proliferation and migration of smooth-muscle cells, this large-scale trial assessed a stent that slowly released the cytotoxic drug paclitaxel, and found that it was safe and that it markedly reduced the rates of restenosis compared with bare-metal stents.

Regenerative Medicine

Dedifferentiation of lineage-committed cells by a small molecule. Chen, S. et al. J. Am. Chem. Soc. 126, 410–411 (2004).

The therapeutic potential of progenitor cells in cell-replacement therapy — for example, in neurodegenerative diseases — has attracted considerable attention, but a key problem is obtaining appropriate cells. The ability to dedifferentiate lineage-committed cells might overcome this problem, and Chen et al. have identified a small molecule that causes mouse muscle cells to dedifferentiate into progenitor cells, which can then redifferentiate into bone or fat cells.