Comparison of cathepsin protease activities in brain tissue from normal cases and cases with Alzheimer's disease, Lewy body dementia, Parkinson's disease and Huntington's disease.
Recent evidence, based upon immunocytochemical and histochemical analysis of brain cortical tissue from alzheimer's disease patients, has suggested that altered activity and/or distribution of the lysosomal proteases cathepsins B and D may be implicated in the abnormal protein processing pathway resulting in formation of the neurotoxic amyloid A4 peptide, characteristic of this neurodegenerative disorder. We have therefore compared, via biochemical assay techniques using conventional or specially synthesised (corresponding to protein cleavage points of relevant to A4 peptide formation) fluorogenic substrates, the levels of activity of the lysosomal proteases cathepsins B, D, H and L, and dipeptidyl aminopeptidases I and II in frontal cortex (grey/white matter) from control and Alzheimer's disease patients. For comparative purposes, activity levels of the above enzymes were also determined in frontal cortex tissue from cases with Lewy body dementia and Parkinson's disease, and in caudate tissue from control and Huntington's disease cases. There was no significant difference in activity for any protease types in tissue from control cases and cases with Alzheimer's disease, Lewy body dementia or Parkinson's disease, with the exception of reduced dipeptidyl aminopeptidase II activity in Lewy body dementia and Parkinson's cases. We have therefore been unable to confirm a potential role for lysosomal cathepsins in the characteristic neurodegeneration associated with Alzheimer's disease; however the finding of significant increases in activity of dipeptidyl aminopeptidase II, cathepsin H and cathepsin D specifically in cases with Huntington's disease is of particular note. We therefore suggest the potential role of the latter enzymes in the pathogenesis of Huntington's disease requires further investigation.
Mantle
D
D
Department of Neurochemistry, Newcastle General Hospital, Newcastle upon Tyne, UK.
Falkous
G
G
Ishiura
S
S
Perry
R H
RH
Perry
E K
EK
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D000595:Amino Acid Sequence; D001921:Brain / Q000201:enzymology*; D002403:Cathepsins / Q000378:metabolism*; D003704:Dementia / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000201:enzymology* / Q000473:pathology; D010300:Parkinson Disease / Q000201:enzymology / Q000473:pathology
D002403:Cathepsins