Alzheimer’s disease and diabetes: hope

for inhibitors against amyloid plaques

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:

1. 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.
2. Gouras, G. K., Olsson, T. T., & Hansson, O. (2015). β-amyloid Peptides and Amyloid
Plaques in Alzheimer’s Disease. Neurotherapeutics, 12(1), 3-11.
3. 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.

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diabetes-hope-for-inhibitors-against-amyloid-plaques/