Regulation of motor proteins, axonal transport deficits and adult-onset neurodegenerative diseases

Neurobiol Dis. 2017 Sep;105:273-282. doi: 10.1016/j.nbd.2017.04.010. Epub 2017 Apr 11.


Neurons affected in a wide variety of unrelated adult-onset neurodegenerative diseases (AONDs) typically exhibit a "dying back" pattern of degeneration, which is characterized by early deficits in synaptic function and neuritic pathology long before neuronal cell death. Consistent with this observation, multiple unrelated AONDs including Alzheimer's disease, Parkinson's disease, Huntington's disease, and several motor neuron diseases feature early alterations in kinase-based signaling pathways associated with deficits in axonal transport (AT), a complex cellular process involving multiple intracellular trafficking events powered by microtubule-based motor proteins. These pathogenic events have important therapeutic implications, suggesting that a focus on preservation of neuronal connections may be more effective to treat AONDs than addressing neuronal cell death. While the molecular mechanisms underlying AT abnormalities in AONDs are still being analyzed, evidence has accumulated linking those to a well-established pathological hallmark of multiple AONDs: altered patterns of neuronal protein phosphorylation. Here, we present a short overview on the biochemical heterogeneity of major motor proteins for AT, their regulation by protein kinases, and evidence revealing cell type-specific AT specializations. When considered together, these findings may help explain how independent pathogenic pathways can affect AT differentially in the context of each AOND.

Keywords: Alzheimer's disease; Amyotrophic lateral sclerosis; Axonal transport; Dynen; Huntington's disease; Kinases; Kinesin; Neurodegeneration; Parkinson's disease; Signaling.

Publication types

  • Review

MeSH terms

  • Animals
  • Axonal Transport / physiology*
  • Humans
  • Microtubule-Associated Proteins / metabolism*
  • Molecular Motor Proteins / metabolism*
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / pathology
  • Neurodegenerative Diseases* / physiopathology
  • Signal Transduction / physiology


  • Microtubule-Associated Proteins
  • Molecular Motor Proteins