title: Retrograde axonal transport: pathways to cell death?
abstract: Active transport along the axon is crucial to the neuron. Motor-driven transport supplies the distal synapse with newly synthesized proteins and lipids, and clears damaged or misfolded proteins. Microtubule motors also drive long-distance signaling along the axon via signaling endosomes. Although positive signaling initiated by neurotrophic factors has been well-studied, recent research has focused on stress-signaling along the axon. Here, the connections between axonal transport alterations and neurodegeneration are discussed, including evidence for defective transport of vesicles, mitochondria, degradative organelles, and signaling endosomes in models of amyotrophic lateral sclerosis, Huntington's, Parkinson's and Alzheimer's disease. Defects in transport are sufficient to induce neurodegeneration, but recent progress suggests that changes in retrograde signaling pathways correlate with rapidly progressive neuronal cell death.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19067, USA.
authors.forename: Eran
authors.initials: E
authors.lastname: Perlson
authors.forename: Sandra
authors.initials: S
authors.lastname: Maday
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Fu
authors.forename: Armen J
authors.initials: AJ
authors.lastname: Moughamian
authors.forename: Erika L F
authors.initials: EL
authors.lastname: Holzbaur
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020409:Molecular Motor Proteins