Mitsugumin 29 is transcriptionally induced in senile plaque-associated astrocytes

Brain Res. 2012 Mar 2;1441:9-16. doi: 10.1016/j.brainres.2011.12.062. Epub 2012 Jan 12.

Abstract

Astrocytes associated with beta-amyloid (Aβ)-deposited senile plaques are a common neuropathological feature of Alzheimer's disease (AD). There is little doubt that the association of Aβ with the major component in the central nervous system cells significantly influences disease progression, however, the molecular mechanisms by which Aβ contributes to the astrocyte-mediated neuropathological changes have not been well established. In an effort to identify astrocyte-derived molecules that may be closely associated with exacerbation of AD, we identified a novel Aβ-induced rat gene, whose mouse counterpart, mitsugumin 29 (MG29), is known to be involved in intracellular Ca²⁺ homeostasis in skeletal muscle. To evaluate the roles of human MG29 in AD, we investigated its expression in AD brain. In non-AD brains, MG29 mRNA has been detected in neurons, but not in quiescent astrocytes. On the contrary, in AD brains, MG29 is expressed in activated astrocytes associated with senile plaques, but not expressed in neurons around lesions. Human MG29-transfected cells express the protein in the endoplasmic reticulum and the level of expression is involved in Ca²⁺-dependent exocytosis mechanisms. Increased MG29 expression in senile plaques-associated activated astrocytes suggests that intracellular Ca²⁺ turnovers may be changed in these astrocytes. This might be related in sustained Ca²⁺-dependent exocytosis of various transmitters including glutamate, leading to the acceleration of neurodegeneration in the lesion observed in AD.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Cell Line, Tumor
  • Cells, Cultured
  • Female
  • Gene Expression Regulation / physiology
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Molecular Sequence Data
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / genetics*
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / metabolism*
  • Plaque, Amyloid / pathology
  • Rats
  • Rats, Wistar
  • Synaptophysin / biosynthesis
  • Synaptophysin / genetics*
  • Transcription, Genetic / genetics*

Substances

  • Mg29 protein, mouse
  • Muscle Proteins
  • Synaptophysin