Cyclin-dependent kinase 5 and mitogen-activated protein kinase in glial cytoplasmic inclusions in multiple system atrophy

J Neuropathol Exp Neurol. 1998 Jul;57(7):690-8. doi: 10.1097/00005072-199807000-00006.

Abstract

Glial cytoplasmic inclusions (GCI) characteristically occur in the oligodendrocytes of patients with multiple system atrophy (MSA). However, the molecular mechanisms underlying GCI formation are unknown. To investigate whether these inclusions are related to proline-directed protein kinases that have been associated with neuronal inclusion bodies in some other neurodegenerative diseases, we immunohistochemically probed tissue samples from MSA brains with a panel of antibodies against cyclin-dependent kinases and mitogen-activated protein kinase. We unexpectedly detected cyclin-dependent kinase 5- (cdk5) and mitogen-activated protein kinase- (MAPK) immunoreactivities in GCI. We also found TAU1 immunoreactivity in GCI, and a strong expression of microtubule-associated protein (MAP) 2 immunoreactivity in oligodendrocytes of MSA brains. This immunoreactivity was not observed in the normal or neurological controls. The accumulated evidence suggest a close association between GCI and the microtubular cytoskeleton. Cdk5 phosphorylates tau and MAP2, and MAPK is capable of phosphorylating MAP2. The present results suggest that the aberrant or ectopic expression of cdk5 and MAPK causes abnormal phosphorylation of microtubular cytoskeletal proteins, thus leading to GCI formation in affected oligodendrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / enzymology
  • Amyotrophic Lateral Sclerosis / pathology
  • Axons / ultrastructure
  • Brain / enzymology
  • Brain / pathology*
  • Calcium-Calmodulin-Dependent Protein Kinases / analysis*
  • Cyclin-Dependent Kinase 5
  • Cyclin-Dependent Kinases*
  • Female
  • Humans
  • Inclusion Bodies / enzymology*
  • Inclusion Bodies / pathology
  • Male
  • Middle Aged
  • Multiple System Atrophy / enzymology*
  • Multiple System Atrophy / pathology
  • Neuroglia / enzymology*
  • Neuroglia / pathology
  • Olivopontocerebellar Atrophies / enzymology
  • Olivopontocerebellar Atrophies / pathology
  • Protein Serine-Threonine Kinases / analysis*
  • Shy-Drager Syndrome / genetics
  • Shy-Drager Syndrome / pathology
  • Supranuclear Palsy, Progressive / enzymology
  • Supranuclear Palsy, Progressive / pathology

Substances

  • Cyclin-Dependent Kinase 5
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • CDK5 protein, human
  • Cyclin-Dependent Kinases