Zeitschrift für Molekulare Medizin und Therapeutik

Novel Combinatorial Therapeutic Targeting of PAI-1(SERPINE1) Gene Expression in Alzheimer’s Disease

Stacie M. Kutz, Craig E. Higgins and Paul J. Higgins

Novel Combinatorial Therapeutic Targeting of PAI-1(SERPINE1) Gene Expression in Alzheimer’s Disease

Accumulation of neurotoxic amyloid peptides (Aβ) in the brain, generated by β-site proteolytic processing of the amyloid precursor protein (APP), is the hallmark pathophysiologic feature of Alzheimer’s disease. The plasmin-activating cascade, in which urokinase (uPA) and tissue-type (tPA) plasminogen activators convert plasminogen to the broad-spectrum protease plasmin, appears to serve a protective, Aβ-clearing, role in the central nervous system.