Amyloid self-assembly is linked to the pathogenesis of Alzheimer’s disease (AD) and type Ⅱ diabetes (T2D), Several teams of scientists around the world are working on finding ways to prevent amyloid plaque formation in the human brain, but so far none of the anti-amyloid molecules has reached the clinic. Scientists at the Technical University of Munich (TUM) have now come a little bit closer to a solution: They have described a new class of designed macrocyclic peptides (MCIPs) that are highly potent inhibitors of amyloid formation. Related research published in the international magazine Angewandte Chemie International Edition. In its new study, the team presents macrocyclic peptides, developed as a new class of amyloid inhibitors. “We have discovered an MCIP that is stable in human blood plasma and can also overcome the human blood-brain barrier in an in vitro cell culture model,” explains Professor Kapurniotu. She adds: “So far we were ‘only’ able to demonstrate these properties in the test tube – thus further research is necessary. But these are two highly desirable properties for inhibitors of Alzheimer’s amyloid.”
The relationship between β-amyloid and AD, TDM2
Many lines of evidence support that β-amyloid (Aβ) peptides play an important role in Alzheimer’s disease (AD), the most common cause of dementia. Aβ peptides are generated through the proteolytic cleavage of amyloid precursor protein (APP), a transmembrane protein, by enzyme complexes α, β and γ-secretases. Alzheimer’s disease (AD), which is the most common age-dependent neurodegenerative disease, is characterized by the presence of amyloid deposition, neurofibrillary tangles, progressive loss of synapses, and severe cognitive dysfunction. Excessive accumulation of β-amyloid peptides (Aβ) is a widely recognized early event that leads to the development of AD pathologies, including impairments in synaptic functions at various sites. Type II diabetes mellitus (TDM2) is associated with an increased risk of cognitive dysfunction and dementia. Insulin also regulates the metabolism of β-amyloid and tau, the building blocks of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer’s disease.
Conclusion
In the more than 20 years that the amyloid hypothesis has been formally articulated, a wealth of studies from many laboratories worldwide has supported its broad outlines. The development of anti-Aβ therapeutics remains a rational approach to treating AD and TDM2, based on current understanding and research of the earliest features of this disease. Disease treatment strategies require more research. When starting your project, you may have certain expectations in mind and know exactly the route that you want your project to take. Remember that the Creative peptides has technical expertise and has probably seen a project like yours several times previously so take their advice on board.
References:
- Spanopoulou, A., Heidrich, L., Chen, H. R., Frost, C., Hrle, D., Malideli, E& Rammes, G. (2018). Designed Macrocyclic Peptides as Nanomolar Amyloid Inhibitors Based on Minimal Recognition Elements. Angewandte Chemie International Edition.
- Gouras, G. K., Olsson, T. T., & Hansson, O. (2015). β-amyloid Peptides and Amyloid Plaques in Alzheimer’s Disease. Neurotherapeutics, 12(1), 3-11.
- Hardy, J., & Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. science, 297(5580), 353-356.