Prolonged exposure of cultured cortical neurons to the residue 25–35 fragment of β-amyloid protein, in the presence of dizocilpine, an antagonist of the N-methyl-D-aspartate receptor, and of 6,7-dinitroquinoxaline-2,3-dione, an antagonist of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors, resulted in the expression of the proapoptotic protein Bax and neuronal death. Beta-amyloid protein(25–35)-induced neuronal death was substantially attenuated by the σ1 receptor agonist 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate. The neuroprotective action of 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate was mimicked by the σ1 ligand methyl (1S,2R)-2-[1-adamantyl(methyl)amino]methyl-1-phenylcyclopropanecarboxylate and was antagonized by the σ1 receptor antagonist N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine monohydrochloride. These results suggest that σ1 receptor agonists might function as neuroprotectant agents in Alzheimer's disease.

Bronchopulmonary dysplasia (BPD) is a chronic illness that usually originates in preterm newborns. Generally, BPD is a consequence of respiratory distress syndrome (RDS) which, in turn, comes from the early arrest of lung development and the lack of pulmonary surfactant. The need of oxygen therapy to overcome premature newborns’ compromised respiratory function generates an increasing amount of reactive oxygen species (ROS), the onset of sustained oxidative stress (OS) status, and inflammation in the pulmonary alveoli deputies to respiratory exchanges. BPD is a severe and potentially life-threatening disorder that in the most serious cases, can open the way to neurodevelopmental delay. More importantly, there is no adequate intervention to hamper or treat BPD. This perspective article seeks to review the most recent and relevant literature describing the very early stages of BPD and hyperoxic lung injuries focussing on nuclear factor erythroid derived 2 (Nrf2)/heme oxygenase-1 (HO-1) axis. Indeed, Nrf2/HO1 activation in response to OS induced lung injury in preterm concurs to the induction of certain number of antioxidant, anti-inflammatory, and detoxification pathways that seem to be more powerful than the activation of one single antioxidant gene. These elicited protective effects are able to counteract/mitigate all multifaceted aspects of the disease and may support novel approaches for the management of BPD.

Since their discovery as distinct receptor proteins, the specific physiopathological role of sigma receptors (σRs) has been deeply investigated. It has been reported that these proteins, classified into two subtypes indicated as σ₁ and σ₂, might play a pivotal role in cancer growth, cell proliferation, and tumor aggressiveness. As a result, the development of selective σR ligands with potential antitumor properties attracted significant attention as an emerging theme in cancer research. This perspective deals with the recent advances of σR ligands as novel cytotoxic agents, covering articles published between 2010 and 2020. An up-to-date description of the medicinal chemistry of selective σ₁R and σ₂R ligands with antiproliferative and cytotoxic activities has been provided, including major pharmacophore models and comprehensive structure–activity relationships for each main class of σR ligands.