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Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons

Costa, Rui O.; Martins, Helena; Martins, Luís F.; Cwetsch, Andrzej W; Mele, Miranda; Pedro, Joana R.; Tomé, Diogo; Jeon, Noo Li; Cancedda, Laura

Ribosomes and a subset of cellular mRNAs are trafficked into axons of developing neurons. The axonal localization of translational machinery allows new proteins to be rapidly and locally synthesized during axonal growth and pathfinding. However, in mature neurons, axonal ribosomes are significantly reduced or even absent. The mechanism that elicits this removal is currently unknown. Here, we demonstrate that sy...


Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF

Martins, Luís F.; Costa, Rui O.; Pedro, Joana R.; Aguiar, Paulo; Serra, Sofia C.; Teixeira, Fabio G.; Sousa, Nuno; Salgado, António J.

Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its c...


Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF

Martins, Luís F.; Costa, Rui O.; Pedro, Joana R.; Aguiar, Paulo; Serra, Sofia Cravino; Teixeira, Fábio Gabriel Rodrigues; Sousa, Nuno; Salgado, A. J.

Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its c...


Visualizing K48 Ubiquitination during Presynaptic Formation By Ubiquitination-I...

Pinto, Maria J.; Pedro, Joana R.; Costa, Rui O.; Almeida, Ramiro D.

In recent years, signaling through ubiquitin has been shown to be of great importance for normal brain development. Indeed, fluctuations in ubiquitin levels and spontaneous mutations in (de)ubiquitination enzymes greatly perturb synapse formation and neuronal transmission. In the brain, expression of lysine (K) 48-linked ubiquitin chains is higher at a developmental stage coincident with synaptogenesis. Neverth...


The proteasome controls presynaptic differentiation through modulation of an on...

Pinto, Maria J.; Alves, Pedro L.; Martins, Luís; Pedro, Joana R.; Ryu, Hyun R.; Jeon, Noo Li; Taylor, Anne M.; Almeida, Ramiro D.

Differentiation of the presynaptic terminal is a complex and rapid event that normally occurs in spatially specific axonal regions distant from the soma; thus, it is believed to be dependent on intra-axonal mechanisms. However, the full nature of the local events governing presynaptic assembly remains unknown. Herein, we investigated the involvement of the ubiquitin-proteasome system (UPS), the major degradativ...


Visualizing K48 Ubiquitination during Presynaptic Formation By Ubiquitination-I...

Pinto, Maria J.; Pedro, Joana R.; Costa, Rui O.; Almeida, Ramiro D.

In recent years, signaling through ubiquitin has been shown to be of great importance for normal brain development. Indeed, fluctuations in ubiquitin levels and spontaneous mutations in (de)ubiquitination enzymes greatly perturb synapse formation and neuronal transmission. In the brain, expression of lysine (K) 48-linked ubiquitin chains is higher at a developmental stage coincident with synaptogenesis. Neverth...


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