rifampin and Parkinson-Disease

Besides its well known antibiotic activity rifampicin exerts multiple brain protective functions in acute cerebral ischemia and chronic neurodegeneration. The present mini-review gives an update of the unique activity of rifampicin in different diseases including Parkinson's disease, meningitis, stroke, Alzheimer's disease and optic nerve injury.

Topics: Alzheimer Disease; Animals; Antibiotics, Antitubercular; Brain; Humans; Meningitis; Neuroprotective Agents; Optic Nerve Injuries; Parkinson Disease; Receptors, Glucocorticoid; Rifampin; Stroke

Rifampicin is a macrocyclic antibiotic used extensively for the treatment of Mycobacterium tuberculosis and other mycobacterial infections. Recently, it was discovered that rifampicin exhibits neuroprotective effects. It has been shown to protect PC12 cells against MPP(+)-induced apoptosis and inhibit the expression of α-synuclein multimers. In in vitro studies, rifampicin pretreatment protects PC12 cells against rotenone-induced cell death. Qualitative and quantitative analyses uncover that rifampicin significantly suppresses rotenone-induced apoptosis by ameliorating mitochondrial oxidative stress. It reduces microglial inflammation and improves neuron survival. Our results indicate that rifampicin is cytoprotective under a variety of experimental conditions, and suggest that it may be useful in PD therapeutics. It is the aim of this paper to review the experimental neuroprotection data reported using rifampicin with a focus on the molecular and cellular mechanisms of cytoprotective effect in in vitro models of PD.

Topics: Animals; Antiparkinson Agents; Apoptosis; Humans; Neurons; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Rifampin

An antibiotic used to treat leprosy is surprisingly effective against Parkinson's disease.

Topics: Humans; Mutation; Nerve Tissue Proteins; Neuroprotective Agents; Parkinson Disease; Rifampin; Synucleins

The aggregation of alpha-synuclein in the dopaminergic neurons of the substantia nigra is a critical step in the Parkinson's disease (PD). The etiology of the disease is unknown but recent epidemiological and experimental studies have renewed interest in the hypothesis that environmental factors, especially herbicides and metals, have a role on the pathogenesis of PD. For the first time, the association constants of alpha-synuclein with five herbicides have been calculated using a capillary electrophoresis (CE) method. In addition, the effect of a number of metals on this binding has been investigated. It appears that the herbicides preferentially bind to a partially folded intermediate conformation of alpha-synuclein induced by manganese, aluminium, cadmium, copper and zinc. Then, metal increases the synuclein-herbicide association. However, this study shows contrasting actions with the antibiotic rifampicin and magnesium addition leading to a decrease of the alpha-synuclein-herbicide interaction even if other metals are present in the bulk solvent. Considering epidemiological studies, all these results suggest an underlying molecular basis for PD and related body diseases.

Topics: alpha-Synuclein; Electrophoresis, Capillary; Environmental Pollutants; Herbicides; Humans; Magnesium; Metals; Nerve Tissue Proteins; Parkinson Disease; Rifampin; Synucleins

alpha-Synuclein aggregation into fibrils is associated with the pathogenesis of Parkinson's disease (PD). Li et al. provide strong evidence that rifampicin interacts with alpha-synuclein and inhibits its fibrillization. Rifampicin could be a promising candidate for therapeutic application for PD.

Topics: alpha-Synuclein; Drug Delivery Systems; Humans; Nerve Tissue Proteins; Parkinson Disease; Rifampin; Synucleins

We studied the relationship between levodopa response and antituberculous treatment in a patient with idiopathic Parkinson's disease whose parkinsonism deteriorated when treatment with rifampicin and isoniazid (Rifinah) for pulmonary tuberculosis was started. A levodopa challenge test with regular recording of motor function was performed during, and again after stopping, antituberculous treatment. Plasma levodopa and levodopa metabolite pharmacokinetic profiles were determined using standard techniques. "On" period duration was 75% longer after antituberculous treatment had been stopped. These clinical findings correlated with a 37% increase in area under the concentration versus time curve (AUC), a 103% increase in apparent elimination half-life (t1/2), a 41% increase in time to maximum concentration (Tmax), and a 33% decrease in maximum concentration (Cmax) of levodopa. A concurrent increase in plasma 3-O-methyldopa (3-OMD) and a decrease in plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the three major metabolites of levodopa, suggests an inhibition of the enzyme dopa decarboxylase, probably by isoniazid.

Topics: 3,4-Dihydroxyphenylacetic Acid; Antitubercular Agents; Dopa Decarboxylase; Homovanillic Acid; Humans; Isoniazid; Levodopa; Male; Middle Aged; Parkinson Disease; Rifampin; Tuberculosis, Pulmonary