Endosomal transport of neurotrophins: Roles in signaling and neurodegenerative d

[Guest guest]

Dev Neurobiol. 2007 May 18

Endosomal transport of neurotrophins: Roles in signaling and

neurodegenerative diseases.

Bronfman FC, Escudero CA, Weis J, Kruttgen A.

Center for Cellular Regulation and Pathology, Department of

Physiology, Faculty of Biological Sciences, Pontificia Universidad

Catolica de Chile, Santiago, Chile.

The internalization and retrograde axonal transport of neurotrophin

receptors is important for their retrograde signal transduction

supporting neuronal differentiation, plasticity, and survival. To

influence transcription, neurotrophin signals initiated at synapses

have to be conveyed retrogradely to the cell body. Signaling

endosomes containing neurotrophin receptor signaling complexes

mediate retrograde neurotrophin signaling from synapses to the

nucleus.

Interestingly, many neurodegenerative diseases, including

Alzheimer's disease, Niemann Pick disease Type C, and Charcot-Marie-

Tooth neuropathies, show alterations of vesicular transport,

suggesting that traffic jams within neuronal processes may cause

neurodegeneration.

Although most of these diseases are complex and may be modulated by

diverse pathways contributing to neuronal death, altered

neurotrophin transport is emerging as a strong candidate influence

on neurodegeneration. In this article, we review the mechanisms of

internalization and endocytic trafficking of neurotrophin receptors,

and discuss the potential roles of perturbations in neurotrophin

trafficking in a number of neurodegenerative diseases.