metalloproteinase
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What about antibiotics for the treatment of the dyskinesia induced by L-DOPA?
L-DOPA-induced dyskinesia is a debilitating adverse effect of treating Parkinson’s disease with this drug. New therapeutic approaches that prevent or attenuate this side effect is clearly needed. Wistar adult male rats submitted to 6-hydroxydopamine-induced unilateral medial forebrain bundle lesions were treated with L-DOPA (oral or subcutaneous, 20 mg kg-1) once a day for 14 days. After this period, we tested if doxycycline (40 mg kg-1, intraperitoneal, a subantimicrobial dose) and COL-3 (50 and 100 nmol, intracerebroventricular) could reverse LID. In an additional experiment, doxycycline was also administered repeatedly with L-DOPA to verify if it would prevent LID development. A single injection of doxycycline or COL-3 together with L-DOPA attenuated the dyskinesia. Co-treatment with doxycycline from the first day of L-DOPA suppressed the onset of dyskinesia. The improved motor responses to L-DOPA remained intact in the presence of doxycycline or COL-3, indicating the preservation of L-DOPA-produced benefits. Doxycycline treatment was associated with decreased immunoreactivity of FosB, cyclooxygenase-2, the astroglial protein GFAP and the microglial protein OX-42 which are elevated in the basal ganglia of rats exhibiting dyskinesia. Doxycycline also decreased metalloproteinase-2/-9 activity, metalloproteinase-3 expression and reactive oxygen species production. Metalloproteinase-2/-9 activity and production of reactive oxygen species in the basal ganglia of dyskinetic rats showed a significant correlation with the intensity of dyskinesia. The present study demonstrates the anti-dyskinetic potential of doxycycline and its analog compound COL-3 in hemiparkinsonian rats. Given the long-established and safe clinical use of doxycycline, this study suggests that these drugs might be tested to reduce or to prevent L-DOPA-induced dyskinesia in Parkinson’s patients.
IMAGING THE TEMPORAL DYNAMICS OF BLOOD-BRAIN BARRIER DYSFUNCTION AND EXTRACELLULAR MATRIX METALLOPROTEINASE INVOLVEMENT AFTER ISCHEMIC STROKE IN RATS
FENS Forum 2026
Leptin regulates the development of glutamatergic synapses in the developing hippocampus through the proteases matrix metalloproteinase 9 and cathepsin B
FENS Forum 2024
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