Amyloidogenesis and Neurotrophic Dysfunction in Alzheimer’s Disease: Do They have a Common Regulating Pathway?

Abstract

The amyloid cascade hypothesis has predominately been used to describe the pathogenesis of Alzheimer’s disease (AD) for decades, as Aβ oligomers are thought to be the prime cause of AD. Meanwhile, the neurotrophic factor hypothesis has also been proposed for decades. Accumulating evidence states that the amyloidogenic process and neurotrophic dysfunction are mutually influenced and may coincidently cause the onset and progress of AD. Meanwhile, there are intracellular regulators participating both in the amyloidogenic process and neurotrophic pathways, which might be the common original causes of amyloidogenesis and neurotrophic dysfunction. In this review, the current understanding regarding the role of neurotrophic dysfunction and the amyloidogenic process in AD pathology is briefly summarized. The mutual influence of these two pathogenesis pathways and their potential common causal pathway are further discussed. Therapeutic strategies targeting the common pathways to simultaneously prevent amyloidogenesis and neurotrophic dysfunction might be anticipated for the disease-modifying treatment of AD.

Exploring the Mechanism of Arctium Lappa L. Leaves in the Treatment of Alzheimer's Disease Based on Chemical Profile, Network Pharmacology and Molecular Docking

“…A𝛽 abnormal deposition triggered neuroinflammatory, tau pathology, oxidative stress and synapse damage. [44,45] Therefore, inhibition of A𝛽 production and promotion of A𝛽 clearance are therapeutic strategies to improve AD. APOE can inhibit the A𝛽 abnormal deposition via promoting A𝛽 protein proteolysis, while RELA reversed this change as an inhibitory transcription factor of APOE.…”