Membrane trafficking in neuronal maintenance and degeneration
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Cellular and Molecular Life Sciences
REVIEW
Membrane trafficking in neuronal maintenance and degeneration Dong Wang • Chih-Chiang Chan • Smita Cherry P. Robin Hiesinger
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Received: 6 August 2012 / Revised: 13 October 2012 / Accepted: 15 October 2012 / Published online: 8 November 2012 Ó The Author(s) 2012. This article is published with open access at Springerlink.com
Abstract Defects in membrane trafficking and degradation are hallmarks of most, and maybe all, neurodegenerative disorders. Such defects typically result in the accumulation of undegraded proteins due to aberrant endosomal sorting, lysosomal degradation, or autophagy. The genetic or environmental cause of a specific disease may directly affect these membrane trafficking processes. Alternatively, changes in intracellular sorting and degradation can occur as cellular responses of degenerating neurons to unrelated primary defects such as insoluble protein aggregates or other neurotoxic insults. Importantly, altered membrane trafficking may contribute to the pathogenesis or indeed protect the neuron. The observation of dramatic changes to membrane trafficking thus comes with the challenging need to distinguish pathological from protective alterations. Here, we will review our current knowledge about the protective and destructive roles of membrane trafficking in neuronal maintenance and degeneration. In particular, we will first focus on the question of what type of membrane trafficking keeps healthy neurons alive in the first place. Next, we will discuss what alterations of membrane trafficking are known to occur in Alzheimer’s disease and other tauopathies, Parkinson’s disease, polyQ diseases, peripheral neuropathies, D. Wang C.-C. Chan S. Cherry P. R. Hiesinger (&) Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA e-mail: [email protected] P. R. Hiesinger Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA Present Address: C.-C. Chan Institute of Physiology, National Taiwan University, Taipei, Taiwan
and lysosomal storage disorders. Combining the maintenance and degeneration viewpoints may yield insight into how to distinguish when membrane trafficking functions protectively or contributes to degeneration. Keywords Autophagy Endosome Lysosome Huntington Alzheimer Parkinson
Membrane trafficking and maintenance: what keeps the healthy neuron alive? Neurons are extraordinarily polarized cells. Both axonal and dendritic branches represent challenges especially with regard to membrane trafficking for both neuronal function and maintenance. Synaptic vesicles outnumber any other membrane compartment on the presynaptic site. Even though neurotransmitter release is an extensively studied process, we still understand little about the generation, sorting, and maintenance of synaptic vesicles [1]. In particular, it is not clear how dysfunctional vesicle proteins or complete vesicles are recognized, sorted, and degraded
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