Bioorganic and Medicinal Chemistry

Multipotent drugs with cholinergic and neuroprotective properties for the treatment of Alzheimer...

Autores: Abdelouhahid Samadi - Jose Marco-Contelles - Elena Soriano - Monica Alvarez-Perez - Mourad Chioua - Alejandro Romero - Laura Gonzalez-Lafuente - Luis Gandía - Jose Maria Roda - Manuela G. Lopez - Mercedes Villaroya - Antonio G. Garcia - Cristobal de los Rios

Abstract: Alzheimer’s disease (AD) is an age-related neurodegenerative process characterized by a progressive loss of cognitive abilities, such as memory, language skills, disorientation, attention, and depression. Although the etiology of AD is still poorly understood, several factors such as amyloid-b (Ab)2 deposits, s-protein aggregation, oxidative stress or low levels of acetylcholine3 are thought to play significant roles in the pathology of the disease.4 In spite of the enormous research effort, an efficient strategy for designing new drugs for the treatment of AD is still lacking.

The cholinergic theory1suggests that the selective loss of cho-linergic neurons in AD results in a deficit of acetylcholine (ACh)in specific regions of the brain that mediate learning and memory functions. Consequently, three acetylcholinesterase (AChE) inhib-itors have been approved for commercial use...

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