Comparison of proline endopeptidase activity in brain tissue from normal cases and cases with Alzheimer's disease, Lewy body dementia, Parkinson's disease and Huntington's disease.
Neuronal death associated with plaque and tangle formation characteristic of Alzheimer's disease (AD) may result from an underlying defect of intracellular protein catabolism. In an attempt to identify the proteolytic enzyme types responsible for aberrant protein processing, we have composed the levels of activity of proline endopeptidase in brain tissue samples (grey/white matter) from frontal, parietal, temporal and occipital lobes, from normal control cases, and cases with AD, Lewy body dementia (LBD), Parkinson's disease (PD) and Huntington's disease (HD). The activity of proline endopeptidase was significantly reduced in AD to approximately 65% of that of corresponding control tissue-this is of note since previous biochemical analyses have in general failed to detect altered activity of other protease types in AD tissues. However, this relatively selective reduction in proline endopeptidase activity in AD tissue (in terms of protease types investigated) is not specific for disease type, since activity was also reduced (65%-70% of control) in tissue samples from LBD, PD and HD cases. The data suggest that reduction in proline endopeptidase activity may be a characteristic of a generalized process of neurodegeneration. Although the precise cellular function of this enzyme in normal/ pathological tissues remains to be determined, the question arises as to whether pharmacological strategies designed to enhance proline endopeptidase activity in brain tissue may improve patient outcome in the above disorders.
Mantle
D
D
Dept of Neurochemistry, Regional Neurosciences Centre, Newcastle General Hospital, Newcastle upon Tyne, UK.
Falkous
G
G
Ishiura
S
S
Blanchard
P J
PJ
Perry
E K
EK
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D003704:Dementia / Q000201:enzymology*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000201:enzymology*; D016631:Lewy Bodies; D008297:Male; D010300:Parkinson Disease / Q000201:enzymology*; D011392:Proline; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*; D014018:Tissue Distribution
D011392:Proline; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases