CLINICAL AND MOLECULAR ASPECTS OF MOTONEURON DISEASES - ANIMAL-MODELS, NEUROTROPHIC FACTORS AND BCL-2 ONCOPROTEIN

Animal models of motor neurone disease (MND) are being increasingly us ed for screening molecules with clinical potential. A number of differ ent treatments to decrease the progression of neuronal cell loss have been proposed; these include: Bcl-2 (B-cell leukaemia oncogene-2), neu rotrophic factors, glutamate receptor inhibitors and Ca2+ channel anta gonists. In this review Yves Sagot, Richard Vejsada and Ann C. Kato fo cus on the effects of neurotrophic factors and Bcl-2, both of which ha ve been shown to prevent cell death in various experimental paradigms. Studies performed in animal models of MND have confirmed the potentia l of these molecules to support motoneurone survival. Some of them hav e been shown to act in synergy and these results are discussed in the context of molecular mechanisms leading to collaborative and synergist ic activities, and also with respect to presumptive subpopulations of motoneurones, which express diverse receptors for neurotrophic factors . Finally, the current status of clinical trials for amyotrophic later al sclerosis using neurotrophic factors will be discussed, as well as recent reports that neurotrophic factors can exert adverse effects on neuronal survival.