IMS-BHU researchers identify novel drug target for treating Alzheimer’s disease

Sunday, February 23, 2014

Varanasi: Researchers at the Institute of Medical Sciences, Banaras Hindu University (IMS-BHU) have identified RhoA as a novel drug target in the treatment of Alzheimer’s disease. The study has been published in the FASEB Journal.

Dr Debabrata Dash

Dr Debabrata Dash, professor and head, department of biochemistry, IMS-BHU, said, “We have discovered a novel drug target of amyloid beta toxicity and Alzheimer’s disease in platelet model. We have found that amyloid beta exercises its activity on a cell through activation of a small GTP-binding protein known as RhoA. When we inhibit RhoA activity by employing pharmacological inhibitors, the toxic effects of amyloid beta are prevented. This information would have significant implications in drug development against Alzheimer’s disease.”

Alzheimer’s disease is the most common cause of cognitive decline and memory loss in the elderly. Although local deposit of a small peptide called ‘amyloid-beta’ is known to be responsible for Alzheimer pathology, the underlying molecular mechanism remains largely obscure. This is the reason why there is no effective therapy against this highly debilitating condition.

Platelets are blood cells that are responsible for stoppage of bleeding at the site of injury. Interestingly, platelets are a major source of amyloid-precursor protein in blood.

Dr Dash and co-workers (Vijay Sonkar and Paresh Kulkarni) at Banaras Hindu University have identified target molecules of amyloid-beta in cells using platelets as peripheral model of neurons.

Their study showed that amyloid-beta was able to strongly stimulate platelets leading to aggregate formation. Intravenous administration of the peptide in mouse accelerated thrombus formation in pulmonary vessels.

The effect of amyloid-beta on platelets was found to be mediated through activation of RhoA, a small GTP-binding protein responsible for cytoskeletal reorganization in cells, and that inhibition of RhoA by a specific pharmacological agent reversed the effects of amyloid-beta on platelets.

In order to understand molecular underpinnings amyloid action, researchers went further to demonstrate phosphorylation of downstream effectors of RhoA, namely MYPT1 and myosin light chain, when the cells were exposed to amyloid-beta.

According to the researchers, patients of Alzheimer’s also have clotting abnormalities, which could be explained by amyloid-beta-induced activation of platelets.

“The findings of this study thus identify RhoA as a novel drug target in the treatment of Alzheimer’s disease, and unravel the possible cause of clotting abnormalities seen in these patients,” said Dr Dash.

Categories: Neurology, RESEARCH

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Comment by Dr S K RAi
2014-02-25 14:06:22

Dear Dr Das,
Sir i congratulate you and your team for wonderful invention. this will help the many patients who are suffering from deadly illness of Alzheimer. You had been my teacher in Biochemistry in IMS BHU .I have done MBBS from IMS BHU in 1994.

Great job

Dr Sanjay Rai

Comment by D. Dash
2014-02-25 23:52:04

Dear Dr. Rai,

Thanks for your words. Yes, I remember you very much.

With best wishes,

D. Dash

Comment by shyama kanungo
2014-03-13 22:07:56

Dear Dr.Dash,
Great News. When could the drug be manufactured for use for targetting the site you have discovered? I remeber your talk(long time back at S.C.B Medical college ) on platelet behaviour relating to “Life after death” high lighting reactivation of aggregated platelets in an atmosphere of high Calcium ions. This i presumed was the reason why the severity of disease in preeclampsia is reduced by administration of high calcium dose (2gm/day)
happy to see this news on your discovery of a breakthrough in the treatment of Alzheimer’s disease.
Congrats once again

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