Schwann cells play pivotal roles in the development and maintenance of the peripheral nervous system. Here, we show that intact sciatic nerve axons of mice contain a small population of ribosomes, which increases by several orders of magnitude when axons are desomatized (severed from their cell bodies). We furthermore demonstrate, using the Wallerian degeneration slow mouse as a model, that Schwann cells transfer polyribosomes to desomatized axons. These data indicate that Schwann cells have the propensity to control axonal protein synthesis by supplying ribosomes on local basis.

Axonal degeneration is an active process that has been associated with neurodegenerative conditions triggered by mechanical, metabolic, infectious, toxic, hereditary and inflammatory stimuli. This degenerative process can cause permanent loss of function, so it represents a focus for neuroprotective strategies. Several signaling pathways are implicated in axonal degeneration, but identification of an integrative mechanism for this self-destructive process has remained elusive. Here, we show that rapid axonal degeneration triggered by distinct mechanical and toxic insults is dependent on the activation of the mitochondrial permeability transition pore (mPTP). Both pharmacological and genetic targeting of cyclophilin D, a functional component of the mPTP, protects severed axons and vincristine-treated neurons from axonal degeneration in ex vivo and in vitro mouse and rat model systems. These effects were observed in axons from both the peripheral and central nervous system. Our results suggest that the mPTP is a key effector of axonal degeneration, upon which several independent signaling pathways converge. Since axonal and synapse degeneration are increasingly considered early pathological events in neurodegeneration, our work identifies a potential target for therapeutic intervention in a wide variety of conditions that lead to loss of axons and subsequent functional impairment.

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The hallmark event of Alzheimer's disease (AD) is the deposition of amyloid as insoluble fiber masses in extracellular neuritic plaques and around the walls of cerebral blood vessels . The main component of amyloid is a hydrophobic peptide, named amyloid 0-peptide (ßA4), which results from the processing of a much longer membrane amyloid precursor protein (APP) . This review focuses on the structural features of ßA4 and the factors that determine ßA4 insolubilization . Theoretical and experimental studies of the primary structure of /8A4 have shown that it is composed of a completely hydrophobic C-terminal domain, which adopts Q-strand structure, and an N-terminal region, whose sequence permits different secondary structures . In fact, this region can exist as an a-helical or,6-strand conformation depending on the environmental condition (pH and hydrophobicity surrounding the molecule) . The effects of pH and hydrophobicity on ßA4 structure may elucidate the mechanisms determining its aggregation and amyloid deposition in AD . Key Words : Amyloid-,3-structure-Senile plaque-Dementia .