A peculiar severe disease process of the cerebral cortex' are the exact words used by A. Alzheimer in 1906 to describe a patient's increasingly severe condition of memory loss, changes in personality, and sleep disturbance. A century later, this 'peculiar' disease has become widely known as Alzheimer's disease (AD), the world's most common neurodegenerative disease, affecting more than 35 million people globally. At the same time, its pathology remains unclear and no successful treatment exists. Several theories for AD etiology have emerged throughout the past century. In this review, we focus on the metabolic mechanisms that are similar between AD and metabolic diseases, based on the results from genome-wide association studies. We discuss signaling pathways involved in both types of disease and look into new optogenetic methods to study the in vivo mechanisms of AD.

Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT and α adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT and adrenergic α receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5-HT and α receptors with (R)-isolaureline showing the greatest potency (pK = 8.14 at the 5-HT receptor). Both (R)- and (S)-glaucine also antagonized α receptors, but they behaved very differently to the other compounds at 5-HT receptors: (S)-glaucine acted as a partial agonist at all three 5-HT receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT receptor.

In this study, the ()-enantiomers of the aporphine alkaloids, nuciferine and roemerine, were prepared a synthetic route involving catalytic asymmetric hydrogenation and both stereoisomers were evaluated for functional activity at human 5-HT and adrenergic α receptor subtypes using a transforming growth factor-α shedding assay. Both enantiomers of each of the compounds were found to act as antagonists at 5-HT and α receptors. ()-roemerine was the most potent compound at 5-HT and 5-HT receptors (p = 7.8-7.9) with good selectivity compared to ()-roemerine at these two receptors and compared to its activity at 5-HT, α, α and α receptors.