Differential distribution of messenger RNAs for cathepsins B, L and S in adult rat brain: An in situ hybridization study

Abstract

The cysteine lysosomal proteases comprise a large family of highly conserved enzymes which are essential for intracellular protein turnover. These proteases are very efficient in their ability to degrade components of the extracellular matrix, and have been implicated in processes of cell growth, malignant transformation and inflammation. There is also a growing body of evidence for their involvement in the metabolism of the amyloid precursor protein. The production of insoluble [beta]A4 amyloid peptide is thought to be one of the key events that lead to the development of Alzheimer's pathology.To see the physiological role these enzymes play in the brain, we studied the relative abundance and distribution of the messenger RNAs for three lysosomal cysteine proteases, cathepsins B and L and cathepsin S, by in situ hybridization histochemistry in rat brain. All three enzymes are capable of degracling components of the extracellular matrix but they have different substrate preferences and resistances to neutral pH. We found that the mRNAs for cathepsins B, L, and S have different expression patterns in brain. Cathepsin B mRNA shows the highest level of expression. It has a wide distribution, and is preferentially expressed in neurons. The expression patterns of cathepsin B and cathepsin L mRNA overlap in many brain regions; in some areas they complement each other. Cathepsin B and L mRNAs are highly expressed in the choroid plexus, a structure that is instrumental in brain development. Both transcripts are also abundant in the neuropeptide synthesizing hypothalamic nuclei. Cathepsin S mRNA has wide expression pattern throughout brain, in grey and white matter. A great number of cells that express cathepsin S have microglial morphology.Regions that are known to contain the highest amounts of the amyloid precursor protein express highest levels of cathepsin B and cathepsin L mRNA. Also, all three transcripts are highly represented in regions that are most prone to degeneration in Alzheimer's disease. These results suggest a role for these lysosomal hydrolases released from degenerating cells in the development of Alzheimer's pathology.