{'fraction_non_alphanumeric': 0.014925373134328358, 'fraction_numerical': 0.0009950248756218905, 'mean_word_length': 5.550488599348534, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Diabetic Neuropathy and the Pharmacology of Gangliosides

The onset of polyneuropathy in diabetes is characterized by the appearance of functional abnormalities in both motor and sensory components of nerve. Prominent among these are reduced conduction velocity and increased resistance to ischaemic conduction failure. In advanced cases, there is morphological evidence for both nerve fibre degeneration and regeneration. The pathogenesis of diabetic neuropathy i s unknown, but most probably involves defects in metabolism within the axon and Schwann cells; as well as adverse changes in vascular factors which may result in deprivation of an adequate oxygen supply to the nerve. In animal models of diabetes and to a lesser extent in human patients, a variety of biochemical alterations in nerve have been characterized. A partial list of these includes enhanced flux of glucose metabolism through the polyol pathway, decreased myo-inositol levels, altered phosphoinositide turnover, and diminished 1,2diacylglycerol content. These abnormalities have been hypothesized to be responsible for decreased Na+,K+ATPase activity by a mechanism mediated by protein kinase C. The reduction in Na+ pump activity i s thought to lead to accumulation of this ion within the axon, thereby contributing to the drop in conduction velocity. In addition, both anterograde and retrograde axonal transport exhibit defects and this may account for the axonal atrophy which i s observed due to a decreased proximo-distal movement of cytoskeletal components, especially neurofilaments. Among the therapeutic approaches to experimental diabetic neuropathy that have been explored, ganglioside treatment has proved able to prevent or reverse several of these changes. In this article, we first briefly summarize the pharmacology of gangliosides in relation to their effects on diabetic neuropathy and then discuss our recent findings which may help to shed light on how gangliosides act to alleviate abnormalities in this disorder.