Potential roles of protease inhibitors in Alzheimer's disease

Abraham, Carmela R.

doi:10.1016/0197-4580(89)90097-3

Cited by 18 publications

(14 citation statements)

References 20 publications

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“…However, the absence of correlations between the activity of these CSF enzymes and the psychological test scores or duration of the disease, together with the well established correlation between cognitive impairment and neurofibrillary plaques and tangles [27], support the idea that this change may reflect a general metabolic alteration. Moreover, other studies of aminopeptidase activity in the cerebral cortex of AD patients failed to detect significant changes in Ala-AP activity [2,24,25], which questions the role of these enzymes in the neurodegenerative process of AD.…”

Section: Discussionmentioning

confidence: 99%

“…These lesions may result from an underlying defect of protein degradation [2]. The most significant neurochemical alteration observed is a marked decrease in choline acetyltransferase activity in regions such as hippocampus, caudate nucleus, amygdala and cerebral cortex [3].…”

Section: Introductionmentioning

confidence: 99%

“…Altered proteolytic breakdown may also take part in the formation of plaques and tangles [2,12]. Moreover, both processes may also modify the free amino acid pool.…”

Section: Introductionmentioning

confidence: 99%

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Alanyl-Aminopeptidase Activity Decrease in Cerebrospinal Fluid of Alzheimer Patients

Iribar¹,

Montes²,

Maldonado³

et al. 1997

Dement Geriatr Cogn Disord

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We analyzed the amino acid concentrations and aminopeptidase activities in plasma and the cerebrospinal fluid (CSF) of Alzheimer patients. Correlations were calculated between these parameters and the degree of cognitive impairment, duration of the disease and age. In comparison with a control group, no changes were found in the levels of amino acids in CSF or plasma of Alzheimer patients. Alanyl-aminopeptidase activity was significantly lower in the CSF of Alzheimer patients, whereas no differences in CSF were detected as regards the remaining aminopeptidases. The plasma/CSF ratio for aminopeptidase activities was higher in AD patients than in controls, although the difference was only significant for alanyl-aminopeptidase. Amino acid ratios did not show this general tendency. The correlations between plasma aspartate and glutamate concentrations and the stage of the disease, measured with the Mini Mental State Examination, were studied. Changes in aminopeptidase activities and their role in protein dysfunction underlying Alzheimer disease are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alanyl-Aminopeptidase Activity Decrease in Cerebrospinal Fluid of Alzheimer Patients

Iribar¹,

Montes²,

Maldonado³

et al. 1997

Dement Geriatr Cogn Disord

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“…Firstly, an abnormal response to normal programmed cell death in the form of growth factors or neurite extension factors may occur (Abraham, 1989). APP may be such a factor (Whitson, Selkoe and Cotman, 1989), as may serine proteases such as alpha 1 anti-chymotrypsin (Kitaguchi et al, 1988; Ponte et al, 1988;Tanzi et al, 1988), or glycosaminoglycans (Snow, Willmer and Kisilevsky, 1987).…”

Section: Amyloidmentioning

confidence: 99%

The treatment of Alzheimer's disease

Allen

Burns

1995

J Psychopharmacol

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“…Recent identification of other protease inhibitors present in brain amyloid deposits in Alzheimer disease (48)(49)(50) indicate that control of protease activity may indeed be important to both normal and pathological processes in the aging brain. At present, however, the age-dependent nature of protease-protease inhibitor interactions in brain is not understood.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II induces secretion of plasminogen activator inhibitor 1 and a tissue metalloprotease inhibitor-related protein from rat brain astrocytes.

Olson

Shiverick

Ogilvie

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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The present study investigates angiotensin (Ang) II effects on secretory protein synthesis in brain astrocytes cultured from neonatal and 21-day-old rats. Ang IIinduced changes in the de novo synthesis of [35S]methioninelabeled secretory proteins were visualized using two-dimensional NaDodSO4/PAGE. Astrocytes from 21-day-old rat brain possess specific high-affinity receptors for Ang II. These cells express two Ang 11-induced secretory proteins with M, 55,000 (AISP-55K) and Mr 30,000 (AISP-30K), which were time-and dose-dependent (EC50, 1 nM). [Sar', 11e8]Ang II (where Sar is sarcosine) inhibited Ang II-induced secretion of AISP-55K but not AISP-30K. N-terminal amino acid sequencing indicates that AISP-55K is identical to rat plasmiogen activator inhibitor 1, whereas AISP-30K exhibits 72-81% identity to three closely related proteins: human tissue inhibitor of metalloproteases, a rat phorbol ester-induced protein, and the murine growth-responsive protein 16C8. Immunofluorescent staining with rat plasminogen activator inhibitor 1 antibody was induced in the majority of cells in culture after Ang II treatment of astrocytes from 21-day-old rat brains. Absence of this response to Ang II in astrocytes from neonatal rat brain provides evidence that this action of Ang II on astrocytes is developmentally regulated.The octapeptide angiotensin (Ang) II has in recent years been implicated in the central control of blood pressure. Evidence in support of this view includes observations that centrally injected Ang II causes profound increases in blood pressure, that all components of the renin-Ang system are found in the brain (1-3), and that increased levels of Ang II and Ang II receptors are seen in brains of spontaneously hypertensive rats (4, 5). Cardiovascular effects of Ang II have been attributed to the modulation of sympathetic activity of neurons in relevant cardioregulatory centers of the brain (1, 2). In vitro studies with neurons in primary culture have further shown that occupation of neuronal Ang II receptors modulates both catecholamine synthesis and reuptake (6, 7). Increased levels of Ang II receptors have been found in neurons cultured from spontaneously hypertensive rats (8).In addition to a neuromodulatory role of Ang II, evidence exists for a distinct Ang II system in central nervous system (CNS) astrocytes. Receptors for Ang II (9), angiotensinogen mRNA (10,11), and Ang I and Ang 11 (12,13) have been demonstrated in cultures of astrocytes, and immunoreactive Ang I, Ang II, and angiotensinogen mRNA have been observed in astrocytes in vivo (14-16). Although the presence of an Ang II system in astrocytes is well documented, little is currently understood of its role in normal brain physiology.Recent studies have indicated that intercellular communication between astrocytes and other cells of the brain may be mediated by proteins secreted from astrocytes (17). Cells of astrocytic origin are thought to secrete several neurotrophic factors (18) and the neurotrophic properties of epidermal growth factor ...

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Potential roles of protease inhibitors in Alzheimer's disease

Cited by 18 publications

References 20 publications

Alanyl-Aminopeptidase Activity Decrease in Cerebrospinal Fluid of Alzheimer Patients

Alanyl-Aminopeptidase Activity Decrease in Cerebrospinal Fluid of Alzheimer Patients

The treatment of Alzheimer's disease

Angiotensin II induces secretion of plasminogen activator inhibitor 1 and a tissue metalloprotease inhibitor-related protein from rat brain astrocytes.

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