Apoptosis and muscle fibre loss in neuromuscular disorders

The past decade has witnessed increasing evidence that besides necrosis, apoptotic cell death mechanisms contribute to muscle fibre loss in various neuromuscular conditions, including the muscular dystrophies, metabolic myopathies, and cases of denervation. The up-regulation of bax and bcl-2, both members of the bcl-2 family, indicate that the predominant effectors involve permeability transition pores in the mitochondrial membrane and subsequent caspase activation which confers the typical morphological and biochemical features of apoptosis such as DNA-fragmentation. It is likely that apoptotic degradation of nuclei and contractile elements is a localized event in muscle fibre segments leading to muscle fibre atrophy and finally loss in these disorders. Essential triggers of apoptosis seem to be homeostatic dysregulation as well as oxidative stress, with increased generation of free oxygen radicals and nitric oxide. In the absence of effective primary treatments, there is hope that interventions in muscle fibre apoptosis will bear promising therapeutic strategies. (C) 2002 Elsevier Science B.V. All rights reserved.