Cellular signaling mechanisms common to the development and degeneration of neuroarchitecture. A review.

The present review examines the hypothesis that similar cellular signaling mechanisms are involved in neural development and in age- or disease-associated degeneration. It is hoped that approaching the problem of the regulation of brain structure from this perspective will spur future studies on the links between development, aging and disease. In order for functional neural circuitry to form, the component neurons must interact in highly specific ways. Growth factors and neurotransmitters constitute two major classes of intercellular signals that sculpt neuroarchitecture. These signals influence the neuronal growth cone behaviors which ultimately determine the details of neuritic form. In addition, growth factors and neurotransmitters can influence neuronal survival and synapse formation, and thereby determine both the presence of neurons within circuits and their specific connectivity patterns. Imbalances in growth factor and/or neurotransmitter systems may lead to neurodegeneration in aging and in specific neurodegenerative disorders such as Alzheimer's disease. Developmental, functional and pathological studies of excitatory amino acid neurotransmitters provide a compelling example of how a common intercellular signal can be involved in neuronal development, plasticity and degeneration. Intracellular signaling systems mediate neuroarchitectural responses to neurotransmitters and growth factors by altering the status of the cytoskeletal and vesicular substrates that are the basis of neuronal form. These signal transduction systems include ion channels and second messengers such as calcium, cyclic nucleotides and diacylglycerol. Cytoskeletal and vesicular substrates may be influenced directly by second messenger kinases, or indirectly via actions on the biosynthetic and degradative systems of the cell. Alterations in these various intracellular neuroarchitecture-regulating systems can lead to neurodegeneration. Taken together, the data presented here indicate that similar cellular and molecular mechanisms are involved in nervous system development, function, adaptive plasticity and degeneration.