Alzheimer's disease Inhibitors: Current status and future prospects

Abstract

Alzheimer disease is a major public health problem in the elderly. It is the most predominant, intricate neurodegenerative disorder of the brain, affecting above 20 million individuals global. It is an insanity related disease which is characterized by t-protein aggregation, amyloid- β pledges, oxidative stress and lowered levels of acetylcholine in the brain. It is also believed that the plaques and tangles are mainly responsible for the disease. Presently a few class of drugs such as antioxidants, metal chelators, acetylcholinesterase (AChE) inhibitors, monoamine oxidase inhibitors, anti-provocative drugs and NMDA inhibitors present and offer relief. Presently, acetylcholinesterase inhibitors improve the neurological behaviour by increasing availability of acetylcholine at synapse in the presence of intact cholinergic neurons. The genetic studies have revealed four genes that may be linked to the Alzheimer’s disease. These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). When mutation occur  in anyone of four genes its lead to the formation of plaques by production of the amyloid beta 40 and 42.Ways to reduce the amyloid plaques and inhibit the action by constructing a drug  (1E,4Z,6E)-5-hydroxy-7-(3-hydroxyphenyl)-1-(2-methyl-3,4,4a,8a-tetrahydro-2H-1-benzopyran-8-yl)hepta-1,4,6-trien-3-one and noname 3 as potent inhibitors to PSEN-1 binding domain (aa440).Rivastigmine is a drug which is approved by FDI is mostly used in treatment of Alzheimer disease. It have only two analogues: MOL- I (R=OH) and MOL-III (R=Br) showed good binding energies, low relative free binding energy and high affinities towards AChE in comparison to Rivastigmine. The benefits of specific and selective Alzheimer disease inhibitors are currently under discussion and offer a new perspective for a further development of inhibitors.