Đang chuẩn bị liên kết để tải về tài liệu:
DIABETIC NEUROPATHY: CLINICAL MANAGEMENT - PART 3

Chương này bao gồm việc xác định các kinase protein mitogen kích hoạt như đầu dò giai đoạn đầu của các tác hại của đường dây thần kinh ngoại biên. Họ được kích hoạt bởi các hậu quả trao đổi chất của tăng đường huyết, stress oxy hóa cụ thể, áp lực thẩm thấu | 6 Effectors Sonic Hedgehog and p38 Mitogen-Activated Protein Kinase Sally A. Price Rebecca C. Burnand and David R. Tomlinson SUMMARY This chapter covers the identification of mitogen-activated protein kinases as early stage transducers of the damaging effects of glucose on peripheral nerves. They are activated by several metabolic consequences of hyperglycemia in particular oxidative stress osmotic stress and advanced glycation end products. Inhibition of one group of mitogen-activated protein kinases the p38 group prevents the development of reduced nerve conduction velocity in experimental diabetes such inhibition can also be achieved by an aldose reductase inhibitor giving an explanation for the mechanism underlying the damaging effect of the polyol pathway. The effect of treatment is also described with sonic hedgehog in preventing reduced nerve conduction velocity and normalising expression of genes coding for endoskeletal proteins which may be instrumental in preserving the integrity of the distal axon. Key Words Sonic hedgehog p38 MAP kinase nerve conduction gene expression axonal endoskeleton. INTRODUCTION The development of potential new therapies for diabetic neuropathy has been sporadic over the last 20 years. In general the process has been boosted by a prospective aetio-logical mechanism reaching consensus among scientists together with the development of drugs to counteract it. The polyol pathway and aldose reductase inhibitors provide a classical example. As is shown in Fig. 1 interest in the polyol pathway rose dramatically in the 1980s peaking at around 1990 thereafter there has been a steady decline as clinical findings indicated that the hypothesis was inapplicable to complications at least as a sole explanation of pathogenesis. Subsequently no hypothesis has reached such a consensus and the development of potential novel therapeutics has virtually stalled. This chapter attempts to revitalize the process by proposing two new hypotheses to explain