Use of enzyme inhibitors of the dipeptidylpeptidase IV and/or of the aminopeptidase N and/or pharmaceutical preparations thereof for the prevention or therapy of neurodegenerative diseases

The use of inhibitors (I) of enzyme(s) selected from dipeptidyl peptidase IV (DP IV), alanyl-aminopeptidase (aminopeptidase N: APN) and/or enzymes of the same substrate specificities is claimed for reducing neurodegenerative lesions caused by the formation of aggregates of misfolded proteins (e.g. neurofibrillar tangles (NFT)) and blocking or modulating inflammation caused by such lesions, is new. Independent claims are included for: (1) corresponding therapeutic or prophylactic methods using (I); and (2) pharmaceutical preparations (not restricted to particular activities or applications) containing (I) in combination with conventional carriers, additives and/or auxiliaries. ACTIVITY : Neuroprotective; Antiinflammatory; Nootropic; Antiparkinsonian; Anticonvulsant; Antibacterial. Tests were carried out in transgenic mice expressing the human microtubuli-associated tau protein with the P301L mutation under the control of the mouse prion promoter, which develop age-dependent NFT, neurodegeneration and movement deficiency and are a good model for tauopathy in humans (see Nat. Genet., 2000, 25(4), 4020405). Intraperitoneal administration of combinations of DP IV inhibitors (I-49) and APN inhibitors (bestatin hydrochloride, actinonin) at doses of 5-10 mg/kg or the individual inhibitors at 50 mg/kg every 2 to 3 days significantly reduced the number of NFT in both the entorhinal cortex of one hemisphere and the hippocampus of the contralateral area (no quantitative results given), the reduction being greater using a combination of the two types of enzyme inhibitors. MECHANISM OF ACTION : Dipeptidyl peptidase IV (DP IV) inhibitor; alanyl-aminopeptidase (aminopeptidase N: APN) inhibitor.