Amyloid Beta (Aβ) peptide incompatibility with fibrinogen Results in Alzheimer’s disease

سال انتشار: 1395
محل انتشار: چهاردهمین همایش بیوشیمی فیزیک ایران
کد COI اختصاصی: CBC14_011
زبان مقاله: انگلیسی
تعداد مشاهده: 468

نویسندگان

Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Ebrahim Barzegari

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

Rassoul Dinarvand

epartment of Nanotechnology and Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran ۱۳۱۶۹-۴۳۵۵۱, Iran

Ali Akbar Saboury

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

چکیده

Alzheimer’s disease (AD) is a prevalent progressive neurodegenerative disorder, yet with undefinedorigin. The mostly accepted mechanism for AD pathogenesis is the Aβ hypothesis, stating that increasedgeneration of Amyloid-β protein is responsible for the senile plaques and dementia associated with AD[1]. A milestone in study of AD etiology is the recent discovery that Aβ associates with fibrinogen andinduces alterations in the structure of the fibrin clot, making it resistant to fibrinolysis [2].Designinginhibitory molecules against the interaction of Aβ with fibrinogen could be a promising approach tonormalize any blood clots formed in the brain and increase their lysis. Researchers have also designed aninhibitory molecule (RU505) to suppress the proposed Aβ-fibrinogen interaction. However, the molecularmechanisms of both pathogenic Aβ-fibrinogen association and therapeutic Aβ-RU505 interaction haveremained unknown [3].The present study employs molecular modeling and design methods to investigatethe Aβ interactions contributing to AD progress or its treatment.These tasks are what intended by thepresent study, where a more potent Aβ inhibitor (T-777) is introduced. We then propose a descriptivemodel of the association between Aβ and fibrinogen, plus a mechanistic model for the inhibitory bindingof RU505 and T-777 drug candidates.We found that most of the contacts between the Amyloid-β andfibrinogen are of the hydrogen bonding and hydrophobic nature. Though less frequent, the electrostaticcontacts showed specific patterns on both molecules, which give implications for future drug designstudies.

کلیدواژه ها

Alzheimer’s disease (AD); Amyloid-β; Fibrinogen; AD drug

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