Recent study suggests that protofibril-formation of amyloidogenic proteins (APs) might be involved in evolvability, an epigenetic inheritance of multiple stresses, in various biological systems. In cancer, evolvability of multiple APs, such as p53, γ-synuclein and the members of the calcitonin family of peptides, might be involved in various features, including increased cell proliferation, metastasis and medical treatment resistance. In this context, the objective of this paper is to explore the potential therapeutic benefits of reduced APs evolvability against cancer. Notably, the same APs are involved in the pathogenesis of neurodegenerative disease and cancer. Given the unsatisfactory outcomes of recent clinical trial of Aβ immunotherapy in Alzheimer's disease, it is possible that suppressing the aggregation of individual APs might also be not effective in cancer. As such, we highlight the adiponectin (APN) paradox that might be positioned upstream of AP aggregation in both neurodegenerative disease and cancer, as a common therapeutic target in both disease types. Provided that the APN paradox due to APN resistance under the diabetic conditions might promote AP aggregation, suppressing the APN paradox combined with antidiabetic treatments might be effective for the therapy of both neurodegenerative disease and cancer.
Keywords: APN resistance; Adiponectin (APN) paradox; Amyloidogenic proteins (APs); Evolvability; Neurodegenerative disease; Type 2 diabetes mellitus.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.