Cell adhesion molecules in neural plasticity and pathology: similar mechanisms, distinct organizations?
Brain plasticity and the mechanisms controlling plasticity are central to learning and memory as well as the recovery of function after brain injury. While it is clear that neurotrophic factors are one of the molecular classes that continue to regulate brain plasticity in the adult central nervous system (CNS), less appreciated but equally profound is the role of cell adhesion molecules (CAMs) in plasticity mechanisms such as long term potentiation, preservation of neurons and regeneration. Ironically, however, CAMs can also reorganize the extra-cellular space and cause disturbances that drive the development of brain pathology in conditions such as Alzheimer's disease and multiple sclerosis. Candidate molecules include the amyloid precursor protein which shares many properties of a classical CAM and beta-amyloid which can masquerade as a pseudo CAM. Beta-Amyloid serves as a nidus for the formation of senile plaques in Alzheimer's disease and like CAMs provides an environment for organizing neurotrophic factors and other CAMs. Inflammatory responses evolve in this environment and can initiate a vicious cycle of perpetuated neuronal damage that is medicated by microglia, complement and other factors. Certain CAMs may converge on common signal transduction pathways involving focal adhesion kinases. Thus a breakdown in the organization of key CAMs and activation of their signal transduction mechanisms may serve as a new principle for the generation of brain pathology.
Institute of Brain Aging and Dementia, University of California, Irvine 92697-4550, USA. cwcotman@teri.bio.uci.edu
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Cotman
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D000818:Animals; D006801:Humans; D016023:Integrins / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology
D016023:Integrins; D019006:Neural Cell Adhesion Molecules