BHU researchers a step closer to preventing Alzheimer’s

dash-optimized
Prof. Debabrata Dash (right) and Dr. Paresh Kulkarni have found that fibrinogen acts an antidote against amyloid beta that causes Alzheimer’s.

Researchers from the Department of Biochemistry at the Institute of Medical Sciences, Banaras Hindu University (BHU) are a step closer to preventing Alzheimer’s disease. An effective antidote against amyloid beta peptide that causes Alzheimer’s disease and cerebral amyloid angiopathy has been found.

A team of researchers led by Prof. Debabrata Dash has demonstrated for the first time that when fibrinogen binds to amyloid beta it effectively prevents the peptide from causing any cytotoxic effects. Fibrinogen brings about this by preventing amyloid beta from interacting with cells. The results were published in the journal Molecular Medicine.

There is growing evidence that amyloid beta plays a pivotal role in synaptic loss and neuronal death resulting in cognitive decline and thus Alzheimer’s.

optimized-sonkar-1
Vijay Sonkar, who was with the Institute of Medical Sciences, BHU, is the first author of the paper.

Like neuronal cells, platelets too carry an amyloid precurosor protein and releases them as amyloid beta through the action of an enzyme. “Since platelets are easily accessible unlike neuronal cells and platelets are quite sensitive like neurons and carry many neurotransmitters, platelets are considered as a peripheral model of neurons. So we used platelets to study how fibrinogen prevented amyloid beta from stimulating the platelets,” says Prof. Dash, corresponding author of the paper.

Platelets isolated from blood and suspended in a buffer were strongly activated when amyloid beta was added. But amyloid beta was ineffective in stimulating the platelets when the researchers suspended the platelets in plasma. “So we knew that some component in the plasma was preventing the action of amyloid beta on platelets,” he says. “We finally found that fibrinogen present in the plasma was responsible for preventing amyloid beta from acting on the platelets. The toxicity of neuronal cells was also prevented in the presence of fibrinogen.”

The fibrinogen significantly impaired the association of amyloid beta protein with neurons.A battery of platelet functions was studied in the presence of amyloid beta. In each case, the amyloid beta was found to stimulate the platelets to carry out the functions. “But when we added fibrinogen all the amyloid beta-induced functions of the platelets were prevented,” Prof. Dash says.

They also studied the protective effect of fibrinogen on neuronal cells. The presence of fibrinogen significantly impaired the association of amyloid beta protein with neurons. Fibrinogen even reversed the drop in neuronal cell viability in the presence of amyloid beta.

Unlike amyloid beta, fibrinogen is a huge protein and so cannot cross the blood-brain barrier. “We have identified a sequence on fibrinogen that interacts with amyloid beta,” says Dr. Paresh P. Kulkarni from the Department of Biochemistry at the Institute of Medical Sciences, BHU and one of the authors of the paper. “It is nearly the same size as the amyloid beta. We are trying to identify a smaller molecule which has fibrinogen-like properties and is drug-like so we don’t have it to administer it intravenously.”

“Our study opens up the attractive possibility of designing peptides or small molecules resembling parts of fibrinogen that can cross blood-brain barrier to sequester amyloid beta and thus can act as a novel therapeutic strategy against Alzheimer’s disease,” Prof. Dash says.

Published in The Hindu on October 22, 2016

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Create a website or blog at WordPress.com

Up ↑

%d bloggers like this: