serofendic-acid and Neurodegenerative-Diseases

Topics: Animals; Apoptosis; Caspase 3; Cattle; Diterpenes; Drug Design; Fetus; Free Radicals; Glutamic Acid; Humans; Mitochondria; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Rats

Serofendic acid is a natural neuroprotective molecule found in fetal calf serum. It is able to protect neurons against mechanisms of cell death associated with neurodegenerative disease. Because only trace quantities are present in fetal calf serum and complete chemical syntheses are long and inefficient, its development as a therapeutic agent has been slow. We engineered a heterologous metabolic pathway in

Topics: Diterpenes; Metabolic Networks and Pathways; Neurodegenerative Diseases; Neurons; Streptomyces

Serofendic acid was recently identified as a neuroprotective factor from fetal calf serum. This study was designed to evaluate the neuroprotective effects of an intranigral microinjection of serofendic acid based on behavioral, neurochemical and histochemical studies in hemi-parkinsonian rats using 6-hydroxydopamine (6-OHDA). Rats were injected with 6-OHDA in the presence or absence of serofendic acid, or were treated with serofendic acid on the same lateral side, at 12, 24 or 72 h after 6-OHDA lesion. Intranigral injection of 6-OHDA alone induced a massive loss of tyrosine hydroxylase (TH)-immunopositive neurons in the substantia nigra pars compacta (SNpc). Either simultaneous or 12 h post-administration of serofendic acid significantly prevented both dopaminergic neurodegeneration and drug-induced rotational asymmetry. Immunoreactivities for oxidative stress markers, such as 3-nitrotyrosine (3-NT) and 4-hydroxy-2-nonenal (4-HNE), were markedly detected in the SNpc of rats injected with 6-OHDA alone. These immunoreactivities were markedly suppressed by the co-administration of serofendic acid, similar to the results in vehicle-treated control rats. In addition, serofendic acid inhibited 6-OHDA-induced alpha-synuclein expression and glial activation in the SNpc. These results suggest that serofendic acid protects against 6-OHDA-induced SNpc dopaminergic neurodegeneration in a rat model of Parkinson's disease.

Topics: Adrenergic Agents; Aldehydes; alpha-Synuclein; Animals; Behavior, Animal; Blotting, Western; CD11b Antigen; Cell Count; Cell Line; Disease Models, Animal; Diterpenes; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Functional Laterality; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Male; Neurodegenerative Diseases; Neuroprotective Agents; Oxidopamine; Parkinson Disease, Secondary; Parkinsonian Disorders; Rats; Rats, Wistar; Reactive Oxygen Species; Rotarod Performance Test; Rotation; Substantia Nigra; Synaptophysin; Time Factors; Tyrosine; Tyrosine 3-Monooxygenase