Researchers examine inhibitory mechanism in Alzheimer’s disease

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To forget or to do not forget? Nerve cells develop a special network that is damaged when affected by Alzheimer’s disease. Credit: IPC PAS, Grzegorz Krzyzewski

Alzheimer’s illness (AD) is a form of progressive dementia interfering with everyday living. It is triggered by the decline in the number of brain cells resulting in the deterioration of our mental abilities. Among the primary reasons for the aggravating brain cells condition and even the brain shrinkage are molecules having a specific structure called β-amyloids (Aβ). They are peptides that tend to agglomerate around the nerve cells, becoming poisonous and damage them. Recent research studies, provided by researchers from the Institute of Physical Chemistry, Polish Academy of Sciences, led by dr. Piotr Pieta, give hope for inhibition of the β-amyloids’ toxicity by using the K162 particle. Scientists provide a remarkable protective effect on the biological membranes and discuss its inhibition system.

M like memory

Memory is an important part of our transformation from newborns to grownups. It is among the important procedures occurring in our brain determining who we are. Our memories are kept thanks to nerve cells– nerve cells processing and transmitting info by electrical and chemical signals. Within the formation of new forecasts and interconnections in between them, some memories can stick with us for the whole life. If these neurons are irritated, they can be deteriorated, causing brain volume loss, triggering an even progressive type of dementia. As outcome, it adversely impacts our memory in addition to our thinking and behavior.

Regrettably, lots of people struggle with the harsh and silent memory killer affecting the brain irreversibly, which is AD. It interrupts the interaction among neurons, leading to their swelling, loss of cells’ functions, and following cells’ death. It leads to memory loss and causes severe issues like confusion and impacting the general intellectual ability. Therefore, affected people lose all they have. It can impact even youths, developing AD quietly in the brain for numerous years till offering fatal signs.

A like amyloids, B like the beta version

What is the cause of Alzheimer’s illness, which promotes neuron swelling and intensifies their damage? Among the causes is misfolding and abnormal production of Aβ, which develops in the brain and affects neurons. When Aβ occurs as monomers of a structure abundant in α-helices and random coils, they are readily soluble in water showing neuroprotective abilities and stimulates brain development. Nevertheless, misfolding and overproduction result in the production of a water insoluble Aβ of a structure abundant in β-sheet, which quickly aggregate to form harmful oligomers and damages biological membranes. For that reason, numerous studies are concentrated on inhibiting Aβ aggregation and decreasing the lifetime of harmful Aβ oligomers.

Dr. Piotr Pieta’s group resolved the mechanism of preventing the toxicity of little Aβ oligomers by the molecule with an appealing abbreviation: K162. Scientist focused on molecular-level direct imaging, electrochemical, and molecular dynamics studies to show in detail the Aβ-K162 interactions in the lack and existence of a brain-like design membrane.

“K162 customizes Aβ aggregation by inhibiting harmful Aβ oligomers production and promoting non-toxic Aβ monomers, dimers, and fibrils formation. Unlike other inhibitors, K162 secures neurologically useful Aβ monomers. This unique system of action of K162 might provide an alternative restorative fight strategy against ADVERTISEMENT,” says Dr. Piotr Pieta.

Among the most crucial homes of the K162 molecule is that it can quickly cross the biological membranes and permeate the blood-brain barrier. In addition, once it binds to nerve cells, it safeguards them versus inflammation and neuronal damage. Presently, there are numerous difficulties in effective treatments safeguarding nerve cells from toxic clusters of amyloids, while thanks to the understanding of its inhibition system we are a step better to establish novel therapies. Experimental outcomes were explained in the ACS Chemical Neuroscience on 22nd January 2021.

Researchers determine biochemical process responsible for producing hazardous tau More details: Dusan Mrdenovic et al, Inhibition of Amyloid β-Induced Lipid Membrane Permeation and Amyloid β Aggregation by K162, ACS Chemical Neuroscience (2021 ). DOI: 10.1021/ acschemneuro.0 c00754 Provided by Polish Academy of Sciences

Citation: Researchers examine repressive system in Alzheimer’s illness (2021, April 19) retrieved 20 April 2021 from https://medicalxpress.com/news/2021-04-inhibitory-mechanism-alzheimer-disease.html

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