Lysosomotropic Features and Autophagy Modulators among Medical Drugs: Evaluation of Their Role in Pathologies

The concept of lysosomotropic agents significantly changed numerous aspects of cellular biochemistry, biochemical pharmacology, and clinical medicine. In the present review, we focused on numerous low-molecular and high-molecular lipophilic basic compounds and on the role of lipophagy and autophagy in experimental and clinical medicine. Attention was primarily focused on the most promising agents acting as autophagy inducers, which offer a new window for treatment and/or prophylaxis of various diseases, including type 2 diabetes mellitus, Parkinson’s disease, and atherosclerosis. The present review summarizes current knowledge on the lysosomotropic features of medical drugs, as well as autophagy inducers, and their role in pathological processes.

Findings in redox biology: From H2O2 to oxidative stress

My interest in biological chemistry proceeded from enzymology in vitro to the study of physiological chemistry in vivo. Investigating biological redox reactions, I identified hydrogen peroxide (H2O2) as a normal constituent of aerobic life in eukaryotic cells. This finding led to developments that recognized the essential role of H2O2 in metabolic redox control. Further research included studies on GSH, toxicological aspects (the concept of “redox cycling”), biochemical pharmacology (ebselen), nutritional biochemistry and micronutrients (selenium, carotenoids, flavonoids), and the concept of “oxidative stress.” Today, we recognize that oxidative stress is two-sided. It has its positive side in physiology and health in redox signaling, “oxidative eustress,” whereas at higher intensity, there is damage to biomolecules with potentially deleterious outcome in pathophysiology and disease, “oxidative distress.” Reflecting on these developments, it is gratifying to witness the enormous progress in redox biology brought about by the science community in recent years.

Hermann (Hugh) Blaschko (1900–1993): His fundamental contributions to biochemical pharmacology and clinical medicine

Hermann (Hugh) Blaschko was a biochemical pharmacologist best known for discovering how adrenaline (epinephrine), noradrenaline (norepinephrine), and dopamine were synthesized, stored, and metabolized in adrenomedullary cells and sympathetic nerves. Blaschko’s work not only supported the validity of the concept of neurochemical synaptic transmission but he also made fundamental contributions to the development of drugs used in clinical medicine to treat diseases such as depression, hypertension, and Parkinson's Disease.

The Mechanism of Action of Praziquantel: Six Hypotheses

Despite being one of the most commonly used drugs, the molecular mechanism of action of the anthelmintic praziquantel remains unknown. There are some unusual features of this drug. Critically, widespread resistance to praziquantel has not developed despite decades of use. Here, we set out some challenges in praziquantel research and propose some provocative hypotheses to address these. We suggest that praziquantel may have multiple pharmacologically relevant targets and the effects on these may synergise to produce an overall, detrimental effect on the parasite. Praziquantel also acts on a number of host proteins and we propose that these actions are important in the drug’s overall mechanism. Although the drug is largely used in the treatment of human and domestic animal worm infections, there is a considerable “grey literature” along with some academic studies which may have been overlooked. It appears that praziquantel may be effective against hydra. It may also be effective against some unicellular parasites such as Giardia spp. Further, scientific work on these understudied areas may be useful in understanding the molecular mechanism in Trematoda. The lack of widespread resistance suggests that praziquantel may act, at least in part, on a protein-protein interaction. Altered drug metabolism or enhanced drug efflux are the most likely ways resistance may arise. There is a critical need to understand the biochemical pharmacology of this drug in order to inform the discovery of the next generation of anthelmintic drugs.