Protein S100-A5 (Protein S-100D) (S100 calcium-binding protein A5) [S100D]

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S100-mediated signal transduction in the nervous system and neurological diseases.

This article presents new information regarding the complement/level of S100 family members expressed in the brain and reviews the contribution of brain S100 family members to nervous system function and disease. A total of ten S100 family members are reported in the literature to be expressed in brain -S100A1, S100A2, S100A4, S100A5, S100A6, [[S100A10]], S100A11, [[S100A13]], S100B, and S100Z. Quantitative Northern blot analysis detected no S100A3, S100A8, S100A9 or S100A14 mRNA in mouse brain suggesting that these family members are not expressed in the brain. In addition, there was a 100-fold range in the mRNA levels for the six family members that were detected in mouse brain: S100A1/S100B levels were 5-fold higher than S100A6/[[S100A10]] levels and 100-fold higher than S100A4/[[S100A13]] levels. Five of these six family members (S1100A1, S100A6, [[S100A10]], [[S100A13]], and S100B) exhibited age-dependent increases in expression in adult mice that ranged from 5- to 20-fold. Although previous studies on S100 function in the nervous system have focused on S100B, other family members (S100A1, S100A3, S100A4, S100A5) have been implicated in neurological diseases. Like S100B, intra- and inter-cellular forms of these family members have been linked to cell growth, cell differentiation, and apoptotic pathways. Studies presented here demonstrate that ablation of S100A1 expression in PC12 cells results in increased resistance to Abeta peptide induced cell death, stabilization of intracellular [Ca2 ] homeostasis, and reduced amyloid precursor protein expression. Altogether, these results confirm that S100-mediated signal transduction pathways play an important role in nervous system function/disease and implicate S100A1 in the neuronal cell dysfunction/death that occurs in Alzheimer's disease.

MeSH Terms

  • Aging
  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Animals
  • Apoptosis
  • Brain Chemistry
  • Calcium
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Gene Expression Regulation
  • Homeostasis
  • Mice
  • Mice, Inbred C57BL
  • Nervous System Diseases
  • Nervous System Physiological Phenomena
  • Neurons
  • Peptide Fragments
  • S100 Proteins
  • Signal Transduction


S100 proteins in Corpora amylacea from normal human brain.

Corpora amylacea (C.A.) also named polyglucosan bodies (P.B.) are one of the hallmarks of normal brain aging. Although their functions are not yet clear, C.A. increase in number in patients suffering from neurodegenerative diseases. C.A. contain 88% of hexoses and 4% of proteins. Most of the proteins in C.A. are aging or stress proteins such as heat shock proteins, ubiquitinated proteins and advanced glycation end products which are also proinflammatory products. Stimulated by the potential role played by some S100 proteins in the inflammatory process which may be triggered in C.A., we investigated, by immunohistochemistry, the presence of different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A8, S100A9, [[S100A12]] and S100B) in C.A. from normal human brain. Among the ten S100 proteins analyzed, nine (S100A) were detected in C.A. Three S100 proteins (S100A8, S100A9, [[S100A12]]) which are highly expressed in activated macrophages and used as inflammatory markers were detected in C.A. S100A8 was, in addition, found in thick neuronal processes from the pons. One (S100B) could not be found in C.A. although it was highly expressed in astrocytes. In C.A., the staining intensity was estimated by computer-assisted microscopy and gave the following order: S100A1 congruent withS100A8 congruent with S100A9>S100A5> or =S100A4>[[S100A12]]>S100A6> S100A2=S100A3. The potential inflammatory role played by S100 proteins in C.A. is discussed.

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Antibody Specificity
  • Female
  • Humans
  • Inclusion Bodies
  • Male
  • Middle Aged
  • Neurodegenerative Diseases
  • Pons
  • Reference Values
  • S100 Proteins