Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Johan Sandin¹  Gunnar Nordvall¹  Johan Lundkvist² 

[1]AlzeCure Pharma AB, Huddinge, Sweden

[2]Department of Neurobiology, Care Sciences, and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden

[3]AlzeCure Pharma AB, Huddinge, Sweden

[4]Department of Neurobiology, Care Sciences, and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden

[5]Sinfonia Biotherapeutics AB, Huddinge, Sweden

关键词: gamma-secretase;    gamma-secretase modulator;    GSM;    Alzheimer's disease;    APP;    amyloid-beta;   

DOI  :  10.3389/fnmol.2023.1279740

 received in 2023-08-18, accepted in 2023-09-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Recent clinical data with three therapeutic anti-Aβ antibodies have demonstrated that removal of Aβ-amyloid plaques in early Alzheimer's disease (AD) can attenuate disease progression. This ground-breaking progress in AD medicine has validated both the amyloid cascade hypothesis and Aβ-amyloid as therapeutic targets. These results also strongly support therapeutic approaches that aim to reduce the production of amyloidogenic Aβ to prevent the formation of Aβ-pathology. One such strategy, so-called gamma-secretase modulators (GSM), has been thoroughly explored in preclinical settings but has yet to be fully tested in clinical trials. Recent scientific progress has shed new light on the role of Aβ in Alzheimer's disease and suggests that GSMs exhibit specific pharmacological features that hold great promise for the prevention and treatment of Alzheimer's disease. In this short review, we discuss the data that support why it is important to continue to progress in this class of compounds.

【 授权许可】

Unknown   
Copyright © 2023 Nordvall, Lundkvist and Sandin.