Neurodegenerative disease

Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans.Nass, R. et al. Proc. Natl Acad. Sci. USA 99, 3264–3269 (2002)

The molecular basis of dopamine-neuron vulnerability and cell death in Parkinson's disease is poorly understood. Nass et al. report that exposure of C. elegans to the neurotoxin 6-hydroxydopamine causes selective degeneration of dopamine neurons, as visualized by fluorescent-protein tagging. The model system that was established could be a powerful tool for studying the molecular mechanisms that underlie the degeneration of dopamine neurons in Parkinson's disease, and might also be valuable in screening for neuroprotective agents.

Cancer

Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukaemia.Kantarjian, H. et al. N. Engl. J. Med. 346, 645–652 (2002)

Chronic myelogenous leukaemia (CML) is caused by the BCR–ABL kinase. Imatinib mesylate (Gleevec), a selective inhibitor of this kinase, was approved for the treatment of CML in 2001. Kantarjian et al. assessed the effects of Gleevec in patients with late–chronic-phase CML in whom therapy with interferon-α had failed, and found that it induced high rates of cytogenetic and haematological responses, and prevented disease progression in ∼90% of patients.

Viral infection

Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication.Zhu, H. et al. Proc. Natl Acad. Sci. USA 99, 3932–3937 (2002)

Prostaglandins such as PGE2 elicit a wide range of physiological responses. Zhu et al. show that levels of cyclooxygenase 2 (COX2), a key enzyme in the pathway that synthesizes PGE2, are markedly increased in human cells after infection with human cytomegalovirus (HCMV). Treatment of cells with a selective COX2 inhibitor reduced the production of infectious virus by a factor of > 100, and virus replication was substantially restored when drug-blocked cultures were supplemented with PGE2. These findings indicate that induction of COX2 and synthesis of PGE2 are essential for efficient HCMV replication in human cells.

Cancer

The CLN3 gene is a novel molecular target for cancer drug discovery.Rylova, S. N. et al. Cancer Res. 62, 801–808 (2002)

Defects in the CLN3 gene cause juvenile Batten disease, a neurodegenerative disorder characterized by accelerated apoptotic death of photoreceptors and neurons. By contrast, resistance of tumour cells to apoptosis is a key feature of cancer development. Rylova et al. show that CLN3 is overexpressed in several cancer cell lines and that blocking CLN3 expression using an antisense approach inhibits cancer-cell growth and viability.