Spencer P S, Sabri M I, Schaumburg H H, Moore C L
Ann Neurol. 1979 Jun;5(6):501-7. doi: 10.1002/ana.410050602.
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.
许多化学结构不相关的神经毒性化合物以及几种类型的代谢异常，在人类和动物中会引发极为相似的远端对称性多神经病模式。对实验动物的研究表明，许多中毒性多神经病与中枢神经系统和周围神经系统中易损神经纤维束发生的远端和逆行性轴突变性有关。这被称为中枢 - 周围远端轴索性神经病。作者实验室最近的观察结果，关于（1）实验性中毒性神经病中神经纤维变性的时空演变，以及（2）化学结构不相关的神经毒性化合物对糖酵解酶的抑制作用，指出了许多远端轴索性神经病存在共同的代谢基础。据推测，神经毒性化合物通过抑制维持能量合成所需的神经纤维酶，耗尽轴突中的能量供应。来自神经元胞体的酶再供应无法满足轴突中对酶替代的增加需求，导致远端区域酶浓度下降。这会导致能量依赖性轴突运输的局部阻滞，从而产生一系列病理变化，最终导致远端神经纤维变性。这一观点为研究遗传性和获得性人类及动物多神经病的病因提供了一个可行的假说。
