Amyloid Biomarkers in Conformational Diseases at Face Value: A Systematic Review

Abstract

Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for target cell failure (neurons, β-cells, etc.) represent a challenge to translational medicine and play a multidimensional role as biomarkers and potential therapeutic targets. This systematic review, which follows the PICO and Prisma methods, analyses this new-fangled multidimensionality, its strengths and limitations, and presents the future possibilities it opens up. The nuclear diagnosis methods are immunoassays: ELISA, immunodot, western blot, etc., while the therapeutic approach is focused on pharmaco- and molecular chaperones.

Unpacking the aggregation-oligomerization-fibrillization process of naturally-occurring hIAPP amyloid oligomers isolated directly from sera of children with obesity or diabetes mellitus

“…Biomarker identification of early β-cell failure is multidimensional and encompasses the need for a deep understanding of the aggregation/oligomerization process in vivo , their dynamics and their molecular networks 9 . We avoid the polymorphism of oligomeric species by concentrating on those oligomers with low molecular weight that are related to cellular apoptosis and may have a role to play in the developing stages of metabolic syndrome and diabetes 26,31,32,56,57 .…”

“…The discovery of the amyloid oligomers in the STZ-induced diabetes in rats allows the identification of rIAPP oligomers as biomarkers 26 . This new knowledge leads to the search for markers in humans to be able to give short-time diagnostic results, which is the way to overcome the biomarker dilemma 9 . It also allows to study for the first time RIAO from sera of pediatric patients with obesity or DM and shift the paradigm that the conformational disease are linked to aging 2,71 .…”

Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes

“…We overcame the biomarker dilemma by concentrating on oligomers with low molecular weight and cytotoxicity [20,38]. In order to overcome the limitations of ELISAs, we used a potential universal pretreatment that precipitated the oligomers (RIAO) as previously described [20,31]; it is cost-effective and easy to implement in diagnostic laboratories in hospitals.…”

Phosphorylated resveratrol as a protein aggregation suppressor in vitro and in vivo

“…These non-native aggregates can be toxic and are associated with a variety of conformational diseases such as glaucoma, amyloidosis, Alzheimer's and Parkinson's disease. [5][6][7] While Alzheimer´s disease is not fully understood yet, it becomes apparent that excessive accumulation of amyloid beta protein inside the brain (especially in oligomeric form) contributes to synaptic and mitochondrial failure, oxidative stress and inflammation. All of which manifests in cognitive decline and neuronal loss which is typically observed in Alzheimer´s patients.…”