Study of Whether Neurofilaments Undergo Axonal Transport as Cargo of Microtubules

像整个身体一样，大脑也是由细胞组成的。 神经元，大脑的“思考”细胞是独一无二的，因为它们通过接收和传输电信号的长延伸彼此连接。 传输连接（“轴突”）相当长，并且由内部骨架（“细胞骨架”）维持，该内部骨架由独特的互连纤维网络组成。这些纤维本身是由重复的亚单位组装而成的，这些亚单位在神经元体内制造并通过称为“轴突运输”的过程运输到轴突中。 目前还不清楚主要纤维（“神经丝”NF和“微管”）是如何组织的，以及它们如何进行轴突运输。 然而，很清楚的是，轴突的正常发育（以及整个神经系统的正常发育）取决于发育中的轴突内神经丝和微管的正常运输和积累。此外，在以后的生活中不能维持这些纤维会导致轴突萎缩和与衰老和阿尔茨海默病相关的进行性神经元死亡。 在其他类型的细胞中，微管通过相关的马达样蛋白质相互滑动，使一个微管沿着另一个微管“行走”。 类似的蛋白质被用来将膜包裹的物质包沿沿着微管移动到轴突中。Shea博士及其同事假设，神经丝可能通过类似的相关运动蛋白，作为微管的货物进入轴突。 他们将通过引入削弱微管组装和轴突运输的几个不同方面的药物来验证这一假设。 如果他们的假设是正确的，Shea博士和他的同事预计这些药物也会导致神经丝的轴突运输停止。

Like the entire body, the brain is composed of cells. Neurons, the "thinking" cells of the brain are unique in that they connect to each other by long, extensions which received and transmit electrical signals. The transmitting connections ("axons") are quite long, and are maintained by an internal skeleton (the "cytoskeleton") that is comprised of an unique interconnected network of fibers. These fibers themselves are assembled from repetitive subunits that are manufactured in the neuron's body and transported into the axon by a process called "axonal transport". It remains unclear how the major fibers ("neurofilaments" NFs and "microtubules") are organized and how they undergo axonal transport. What is clear, however, is that the proper development of axons (and therefore that of the entire nervous system) is dependent upon the proper transport and accumulation of neurofilaments and microtubules within developing axons. Furthermore, failure to maintain these fibers during later life can lead to axonal atrophy and the progressive neuronal death associated with aging and Alzheimer's disease. In other cell types, microtubules are known to slide past one another by means of associated motor-like proteins that "walk" one microtubule along another one. Similar proteins are used to move membrane-enclosed packets of material along microtubules into the axon. Dr. Shea and colleagues hypothesize that neurofilaments make their way out into the axon by traveling as cargo of microtubules, perhaps via similar associated motor proteins. They will test this hypothesis by introducing drugs that cripple several distinct aspects of microtubule assembly and axonal transport. If their hypothesis is correct, Dr. Shea and his colleagues anticipate that these drugs will also cause axonal transport of neurofilaments to cease.