Pflanzliche Zystein Proteasen

Plant cysteine proteases - new supportive agents in Alzheimer disease therapy?

Kristofikova Z. and Stastny F.

Prague Psychiatric Centre, Ustavni 91, 181 03 Prague 8,Czech Republic

10 th Anniversary Meeting Alzheimer Europe, 12 – 15 October, 2000, München, Germany 

 Book of Abstracts pp. 83-84

529 KA (18-03-3)

Inflammatory mechanisms play a significant role in the pathogenesis of Alzheimer disease (AD). During last years, a great attention has been focused on potential therapeutic role of antiinflammatory agents, which act through the inhibition of prostaglandin synthesis and inflammatory cytokine release. The proinflammatory molecules are also involved in amyloid beta peptide deposits responsible for amyloid angiopathy in brain microvascular walls. Therefore, application of some plant proteolytic enzymes acting as anti-inflammatory agents is suggested. Moreover, protease-mediated decomposition of the vascular deposits might increase the blood-brain barrier permeability to nutrients and therapeutic agents. We suppose that proteases could be applied as supportive medicaments in AD therapy together with some nootropics. Our experiments in vitro on rat brain homogenates (lipid peroxidation) and on capillaries (low affinity choline uptake, activity of gamma-glutamyl transpeptidase (GGT)) or synaptosomes isolated from rat brains (high-affinity choline uptake, specific binding of (3H) hemicholinium-3) have revealed certain positive changes especially in the case of two plant cysteine proteases bromelain and papain. Moreover, our experiments indicate that both proteases are able to eliminate in vitro actions of amyloid beta peptide 1-40. Under in vivo conditions, acute (intravenous) administration of papain increased soluble GGT activity in the blood plasma whereas the membrane-bound microvascular activity of enzyme was decreased in old rats. The results support our earlier in vitro findings of plant cysteine protease-dependent solubilization of GGT activity in rat cerebral microvessels and in cerebral homogenates from patients with AD. The experimental findings may indicate an increased blood-brain barrier permeability induced by the administration of plant cysteine proteases in aging brain. However, the results of experiments with long-term application of both proteases in vivo (28 days, per rectum) on young and old are not known yet in the present time.