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Trends Neurosci. 2013 Jun;36(6):363-73. doi: 10.1016/j.tins.2013.04.003. Epub 2013 May 2.

Where no synapses go: gatekeepers of circuit remodeling and synaptic strength.

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Department of Cell and Developmental Biology, University of Michigan School of Medicine, 3065 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.


Growth inhibitory molecules in the adult mammalian central nervous system (CNS) have been implicated in the blocking of axonal sprouting and regeneration following injury. Prominent CNS regeneration inhibitors include Nogo-A, oligodendrocyte myelin glycoprotein (OMgp), and chondroitin sulfate proteoglycans (CSPGs), and a key question concerns their physiological role in the naïve CNS. Emerging evidence suggests novel functions in dendrites and at synapses of glutamatergic neurons. CNS regeneration inhibitors target the neuronal actin cytoskeleton to regulate dendritic spine maturation, long-term synapse stability, and Hebbian forms of synaptic plasticity. This is accomplished in part by antagonizing plasticity-promoting signaling pathways activated by neurotrophic factors. Altered function of CNS regeneration inhibitors is associated with mental illness and loss of long-lasting memory, suggesting unexpected and novel physiological roles for these molecules in brain health.

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