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Neurotoxic acrylamide and neurotrophic melanocortin peptides–can contrasting actions provide clues about modes of action?
Author(s) -
EDWARDS P. M.,
SPORELOZAKAT E.,
GISPEN W. H.
Publication year - 1991
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.1991.tb00700.x
Subject(s) - melanocortins , neurotrophin , neuroscience , acrylamide , sprouting , mechanism of action , mechanism (biology) , biology , endocrinology , medicine , melanocortin , chemistry , biochemistry , receptor , hormone , in vitro , botany , organic chemistry , copolymer , polymer , philosophy , epistemology
Experimental acrylamide neuropathy has been studied as a model of degenerative neurological disorders of the ‘dying‐back’ type for over 30 years. Functional, histological, ultrastructural, electrophysiological and biochemical aspects of acrylamide neuropathy have been described and several hypotheses concerning the mode of action proposed. However, the mechanism whereby acrylamide causes axonal degeneration and inhibits nerve sprouting remains unknown. By analogy with agonist/antagonist comparisons used by the pharmacologist, we have reconsidered the acrylamide problem in the light of the opposite effects summarized in Table 1, of neurotrophic peptides related to ACTH/MSH (collectively termed melanocortins). The contrasting effects on sprouting and the eventual quality of repair of mechanically lesioned nerves have suggested a mechanism whereby sprouting may regulate perikaryal adjustments to injury. We have also posed the question as to whether a common biochemical mechanism, namely selective proteolysis of neurofilament protein may underlie the opposing effects of acrylamide and melanocortins on nerve sprouting. This possibility implies a hitherto unknown role for neurofilament protein turnover in neuronal maintenance and repair, a suggestion that may provoke further research and discussion.