SCG10‐related neuronal growth‐associated proteins in neural development, plasticity, degeneration, and aging

Abstract

Neuronal growth-associated proteins (nGAPs) are in general neuron-specific gene products whose expression correlates tightly with neuronal process outgrowth and/or regeneration, and are mostly good downstream targets of neurotrophin stimulation. Expression of genes encoding nGAPs such as GAP-43, SCG10, and stathmin is upregulated following lesioning of cortical and hippocampal regions of the adult rat brain. In the brains of aged animals, however, the magnitude of the response is reduced, whereas the time course of the response is mostly unchanged when compared with that for brains of young ones. Expression of GAP-43 and stathmin is reduced by aging, and is also changed in age-related neurodegenerative conditions such as Alzheimer's disease in humans. Certain nGAPs are induced during long-term potentiation (LTP) and also during critical periods of song-learning and ocular dominance column formation in birds and cats, respectively. Recent evidence further supports the idea that functional synaptic modulation is often associated with remodeling of synaptic structures. These results suggest that neurotrophin-responsive nGAPs serve as molecular markers of neuronal plasticity during development and aging, and that the neuronal plasticity decreases, at least in certain neuronal circuits, in the aged brain and neurodegenerative diseases. Recent findings on the roles of stathmin and SCG10-related proteins in microtubule destabilization and its functional block by phosphorylation further support the importance of the SCG10 family proteins in neuronal cytoskeletal regulation, particularly as to microtubule dynamics. We summarize here a decade of research on SCG10 and its related molecules with special interests to brain aging and disease.

The microtubule destabilizer stathmin mediates the development of dendritic arbors in neuronal cells

“…1). This result is consistent with the previous observation that the level of stathmin decreases during the postnatal development of various brain regions (Mori and Morii, 2002;Sugiura and Mori, 1995).…”

A neuron autonomous role for the familial dysautonomia geneELP1in sympathetic and sensory target tissue innervation

“…For example, recent studies proposed that loss of Elp1 leads to a loss of RE-1-silencing transcription factor (Rest), which in turn leads to an increase in stathmin 2 expression (Stmn2/Scg10), which is normally repressed by Rest. As Stmn2 has a major role in neuron MT destabilization (Mori and Morii, 2002), decreased Rest and consequent increased Stmn2 expression was proposed to account for increased levels of soluble Y-αTub and disorganized MTs in cells with low Elp1 levels. Surprisingly, however, in differentiating Elp1 +/+ and Elp1 KO sympathetic and sensory neurons, we found a significant decrease in Stmn2 in both SCG sympathetic and DRG sensory neurons, and an increase in Rest expression in sympathetic SCG neurons and a slight decrease in DRG sensory neurons.…”

A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia

“…53 Previously, stathmin was found to have altered expression in MK-801 treated rats, a glutamategic schizophrenia animal model. 53 Molecules that interact with stathmin include HSP70 and G proteins, 54 and as such altered levels of these proteins may also be related to cytoskeletal abnormality. Further investigations are necessary to elucidate the precise role of stathmin and the microtubule cytoskeleton in schizophrenia.…”