Protease inhibitors and indolamines selectively inhibit cholinesterases in the histopathologic structures of Alzheimer's disease.
Ann N Y Acad Sci
; 695: 65-8, 1993 Sep 24.
Article
em En
| MEDLINE
| ID: mdl-8239315
ABSTRACT
Neurofibrillary tangles and amyloid plaques express acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in Alzheimer's disease. We had found that traditional AChE inhibitors such as BW284C51, tacrine and physostigmine were more potent inhibitors of the AChE in normal axons and cell bodies than of the AChE in plaques and tangles. We now report that the reverse pattern is seen with indolamines, carboxypeptidase inhibitor, and the nonspecific protease inhibitor bacitracin. These substances are more potent inhibitors of the cholinesterases in plaques and tangles than of those in normal axons and cell bodies. These results show that the enzymatic properties of plaque and tangle-associated cholinesterases diverge from those of normal axons and cell bodies. The selective susceptibility to bacitracin and carboxypeptidase inhibitor indicates that the catalytic sites of plaque and tangle-bound cholinesterases are more closely associated with peptidase or protease-like properties than the catalytic sites of cholinesterases in normal neurons and axons. This shift in enzymatic affinity may lead to the abnormal protein processing which is thought to play a major role in the pathogenesis of AD. The availability of pharmacological and dietary means for altering brain indolamines raises novel therapeutic possibilities for inhibiting the abnormal cholinesterase activity associated with Alzheimer's disease.
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Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
/
Inibidores de Proteases
/
Encéfalo
/
Butirilcolinesterase
/
Inibidores da Colinesterase
/
Emaranhados Neurofibrilares
/
Doença de Alzheimer
/
Indóis
Limite:
Humans
Idioma:
En
Revista:
Ann N Y Acad Sci
Ano de publicação:
1993
Tipo de documento:
Article