Review of Theoretical Studies for Prediction of Neurodegenerative Inhibitors

F.      Prado-Prado; I.      Garcia

doi:10.2174/138955712800493780

Abstract

Alzheimer's disease (AD) is characterized by several pathologies, this disease is a neuropathological lesion in brain. Indeed, a wealth of evidence suggests that β-amyloid is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. AD is the most prevalent form of dementia, and current indications show that twenty-nine million people live with AD worldwide, a figure expected rise exponentially over the coming decades. Clearly, blocking disease progression or, in the best-case scenario, preventing AD altogether would be of benefit in both social and economic terms. However, current AD therapies are merely palliative and only temporarily slow cognitive decline, and treatments that address the underlying pathologic mechanisms of AD are completely lacking. While familial AD (FAD) is caused by autosomal dominant mutations in either amyloid precursor protein (APP) or the presenilin (PS1, PS2) genes. First, we revised 2D QSAR, 3D QSAR, CoMFA, CoMSIA and Docking of β and γ-secretase inhibitors. Next, we review 2D QSAR, 3D QSAR, CoMFA, CoMSIA and docking for GSK-3α and GSK-3β with different compound to find out the structural requirements.

Keywords: QSAR, CoMSIA, COMFA, Docking, β-secretase inhibitors, γ-secretase inhibitors, Alzheimer's disease (AD), BACE1, transmembrane, GSK-3, tyrosinase inhibitors, N-terminus