Abstract:

The brain is the third largest organ in the human body and consists of over 80 billion neurons. Neurons are interconnected by neurite to form a complex neural network that allows the communication of neurons to regulate different body functions and activities. Neurites, including axons and dendrites, are the projections of a neuron from the cell body. Dynamic neurite outgrowth is a fundamental neural process for the establishment and maintenance of the functional nervous system. Unfortunately, neurite damage is often observed after brain injuries and in the early stages of many neurodegenerative diseases and in case of age-related neural degeneration. However, stimulation of neurite regeneration has been a major challenge for brain regenerative medicine. For instance, the axon growth of neurons in the central nervous system (CNS) is suppressed by inhibitory molecules released from the neighboring injured cells such as myelin-associated glycoprotein, neurite outgrowth inhibitor-A, oligodendrocyte-myelin glycoprotein, and chondroitin sulfate proteoglycans. Unlike the neurons of the peripheral nervous system, which are capable of regenerating new growth cones (a specialized structure at the tip of the neurite for initiating neurite elongation) shortly after injuries, retraction bulbs are formed in the axons of injured CNS neurons that restrict the formation of proper connections between these neurons. Additionally, the regenerated axons need to grow across a considerable distance to bypass the areas of injury and consequently achieve reconnections. However, many processes that stimulate axon growth are switched off after brain development. Recent findings suggest that these developmental processes can be “re-activated.” Activating the intrinsic pathways for neurite outgrowth could potentially lead to axon regeneration in CNS neurons. Therefore, understanding the regulatory mechanisms of neurite outgrowth would not only advance our knowledge in brain development but also provide insights into methods of inducing neurite re-outgrowth after brain injuries and in the aftermath of neurodegenerative diseases.