Does a defect of energy metabolism in the nerve fiber underlie axonal degeneration in polyneuropathies?
A number of chemically unrelated neurotoxic compounds and several types of metabolic abnormalities cause strikingly similar patterns of distal symmetrical polyneuropathy in humans and animals. Experimental studies with laboratory species have demonstrated that many toxic polyneuropathies are associated with distal and retrograde axonal degeneration occurring in vulnerable nerve fiber tracts in the central as well as the peripheral nervous system. This has been termed central-peripheral distal axonopathy. Recent observations from the authors' laboratories regarding (1) the spatial-temporal evolution of nerve fiber degeneration in experimental toxic neuropathies and (2) the inhibition of glycolytic enzymes by chemically unrelated neurotoxic compounds point to a common metabolic basis for many distal axonopathies. It is postulated that neurotoxic compounds deplete energy supplies in the axon by inhibiting nerve fiber enzymes required for the maintenance of energy synthesis. Resupply of enzymes from the neuronal soma fails to meet the increased demand for enzyme replacement in the axon, causing the concentration of enzymes to drop in distal regions. This leads to a local blockade of energy-dependent axonal transport, which produces a series of pathological changes culminating in distal nerve fiber degeneration. The idea provides a working hypothesis with which to study the cause of inherited and acquired human and animal polyneuropathies.
D001370:Axonal Transport / Q000187:drug effects; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D004734:Energy Metabolism; D006019:Glycolysis / Q000187:drug effects; D006586:Hexanes / Q000494:pharmacology; D006801:Humans; D008742:Methyl n-Butyl Ketone / Q000494:pharmacology; D008959:Models, Neurological; D009410:Nerve Degeneration; D009412:Nerve Fibers / Q000378:metabolism*; D009422:Nervous System Diseases / Q000139:chemically induced
D006586:Hexanes; D008742:Methyl n-Butyl Ketone