Consequences of Pharmacological BACE Inhibition on Synaptic Structure and Function

Zhu, Kaichuan; Peters, Finn; Filser, Severin und Herms, Jochen (2018): Consequences of Pharmacological BACE Inhibition on Synaptic Structure and Function. In: Biological Psychiatry, Bd. 84, Nr. 7: S. 478-487

Abstract

Alzheimer's disease is the most prevalent neurodegenerative disorder among elderly persons. Overt accumulation and aggregation of the amyloid-beta peptide (A beta) is thought to be the initial causative factor for Alzheimer's disease. A beta is produced by sequential proteolytic cleavage of the amyloid precursor protein. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the initial and rate-limiting protease for the generation of A beta. Therefore, inhibiting BACE1 is considered one of the most promising therapeutic approaches for potential treatment of Alzheimer's disease. Currently, several drugs blocking this enzyme (BACE inhibitors) are being evaluated in clinical trials. However, high-dosage BACE-inhibitor treatment interferes with structural and functional synaptic plasticity in mice. These adverse side effects may mask the therapeutic benefit of lowering the A beta concentration. In this review, we focus on the consequences of BACE inhibition-mediated synaptic deficits and the potential clinical implications.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0006-3223
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198