Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). The enzyme 17β-hydroxysteroid dehydrogenase type 10 (HSD10) is a multifunctional mitochondrial protein that is thought to play a role in the pathophysiology of AD and is one of the targets of new potential AD drugs. The in vitro effects of frentizole, riluzole, AG18051, and 42 novel modulators of HSD10 (potential AD drugs) on citrate synthase (CS) activity, monoamine oxidase (MAO) activity, complex I- or complex II-linked mitochondrial respiratory rate, and complex I activity were measured in isolated pig brain mitochondria. Based on their minimal inhibitory effects on the respiratory rate of mitochondria and CS and complex I activity, six novel compounds were selected for further testing. Assuming that inhibition of MAO-B could be a desirable effect of AD drugs, only AG18051 and one new compound met the criteria for MAO-B inhibition with minimal drug-induced effects on mitochondrial respiration. In conclusion, our in vitro screening of mitochondrial effect of novel potential AD drugs has enabled the selection of the most promising molecules for further testing that are relatively safe in terms of drug-induced mitochondrial toxicity.

• MeSH
• 17-Hydroxysteroid Dehydrogenases antagonists & inhibitors   toxicity   MeSH
• Cell Respiration drug effects   MeSH
• Enzyme Inhibitors therapeutic use   toxicity   MeSH
• Humans MeSH
• Mitochondria drug effects   MeSH
• Models, Animal MeSH
• Neurodegenerative Diseases drug therapy   MeSH
• Swine MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• Keywords
• Biochemická lateralita mozku,
• MeSH
• 17-Hydroxysteroid Dehydrogenases isolation & purification   adverse effects   MeSH
• Alzheimer Disease MeSH
• Diagnostic Techniques, Neurological trends   utilization   MeSH
• Hippocampus chemistry   physiopathology   pathology   MeSH
• Humans MeSH
• Meta-Analysis as Topic MeSH
• Disease Models, Animal MeSH
• Neurodegenerative Diseases * diagnosis   complications   prevention & control   MeSH
• Nitric Oxide isolation & purification   metabolism   adverse effects   MeSH
• Oxidative Stress physiology   genetics   immunology   MeSH
• Rats, Long-Evans MeSH
• Rats, Sprague-Dawley MeSH
• Rats, Wistar MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Aging MeSH
• Statistics as Topic MeSH
• Models, Theoretical * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Multifunctional mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 plays a role in the development of Alzheimer's disease. However, changes in its expression in the brain or cerebrospinal fluid are not fully specific for this type of dementia. Our previous study revealed that complexes of the enzyme and amyloid β in cerebrospinal fluid could serve as a more specific biomarker of Alzheimer's disease than either the enzyme or amyloid β individually when compared to autoimmune multiple sclerosis. In this study, enzyme-linked immunosorbent assay and the surface plasmon resonance biosensor method were used to analyse cerebrospinal fluid of patients with various neuroinflammatory diseases. Significant differences in the levels of the total enzyme, complexes, amyloid β 1-42 and total τ/phospho-τ were found in Alzheimer's disease patients while differences in complexes, total amyloid β and amyloid β 1- 42 were observed in patients with neuroinflammatory diseases (except for multiple sclerosis) when compared to non-neuroinflammatory controls. The interactions of the enzyme with amyloid β appeared to depend strongly on neuroinflammation-sensitive amyloid β. Our data demonstrated that oligomerisation/aggregation of intracellular amyloid β peptides was important in Alzheimer's disease while extracellular amyloid β could play a role in neuroinflammatory diseases. Phospho-τ is currently the best biomarker of Alzheimer's disease.

• MeSH
• 17-Hydroxysteroid Dehydrogenases MeSH
• Alzheimer Disease complications   MeSH
• Amyloid beta-Peptides MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Humans MeSH
• Central Nervous System Diseases complications   MeSH
• Vascular Diseases complications   MeSH
• Peripheral Nervous System Diseases complications   MeSH
• Statistics, Nonparametric MeSH
• Peptide Fragments MeSH
• Surface Plasmon Resonance MeSH
• Aged MeSH
• Inflammation complications   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH