POLYNEUROPATHIES AND CNS PROTEIN METABOLISM

Abstract

A defect in neuronal protein metabolism has been proposed as one of the primary, molecular events underlying the development of polyneuropathies of the dying back type. Using acrylamide-intoxication as an experimental model to study these polyneuropathies, changes in leucine-incorporation into proteins disability. Proteinsynthesis rates were determined in vivo using flooding concentrations of [1-14C]valine as the precusor. Under conditions of acute and of chronic intoxication, a decrease in synthesis rate was measured preceding the loss of functional ability. Similar changes in protein synthesis rate were observed in peripheral tissues such as heart muscle and liver showing the general toxicity of acrylamide. Methylene bisacrylamide, that was used to discriminate between the neurotoxic action of acrylamide and its systemic effects, interfered with protein synthesis rates in a comparable way. No change in protein synthesis rate was observed under in vitro conditions suggesting that the interference of acrylamide with the synthetic machinery for protein synthesis in vivo is mediated by one or more as yet unknown indirect factors.