Role of Intracellular Amyloid beta as Pathway Modulator, Biomarker, and Therapy Target

Villarejo, Lucia Gallego; Bachmann, Lisa; Marks, David; Brachthaeuser, Maite; Geidies, Alexander und Mueller, Thorsten (2022): Role of Intracellular Amyloid beta as Pathway Modulator, Biomarker, and Therapy Target. In: International Journal of Molecular Sciences, Bd. 23, Nr. 9, 4656

Abstract

The beta- and gamma-secretase-driven cleavage of the amyloid precursor protein (APP) gives rise to the amyloid beta peptide, which is believed to be the main driver of neurodegeneration in Alzheimer's disease (AD). As it is prominently detectable in extracellular plaques in post-mortem AD brain samples, research in recent decades focused on the pathological role of extracellular amyloid beta aggregation, widely neglecting the potential meaning of very early generation of amyloid beta inside the cell. In the last few years, the importance of intracellular amyloid beta (iA beta) as a strong player in neurodegeneration has been indicated by a rising number of studies. In this review, iA beta is highlighted as a crucial APP cleavage fragment, able to manipulate intracellular pathways and foster neurodegeneration. We demonstrate its relevance as a pathological marker and shed light on initial studies aiming to modulate iA beta through pharmacological treatment, which has been shown to have beneficial effects on cognitive properties in animal models. Finally, we display the relevance of viral infections on iA beta generation and point out future directions urgently needed to manifest the potential relevance of iA beta in Alzheimer's disease.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch