Perindopril Shows Neuroprotective Effects Against Parkinson Disease

Researchers in Japan have found that the angiotensin-converting enzyme (ACE) inhibitor perindopril can protect against neurodegeneration in a mouse model of Parkinson disease. The study, led by R. Kurosaki, evaluated the effects of perindopril on the dopaminergic system in mice after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that perindopril had a dose-dependent neuroprotective effect against MPTP-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) depletion.

Key Takeaways:

• Perindopril, an ACE inhibitor, has been shown to have beneficial effects on the dopaminergic system in mice with Parkinson disease-like symptoms.
• Administration of perindopril resulted in a dose-dependent reduction in MPTP-induced striatal dopamine and DOPAC depletion.
• Perindopril significantly attenuated MPTP-induced substantia nigra and striatal damage, as shown by immunohistochemical studies with various antibodies.
• The protective effect of perindopril may be caused by the reduction of free radicals caused by MPTP.
• Perindopril also blocked the increases in GFAP-positive astrocytes in the striatum and substantia nigra after MPTP treatment.
• The study demonstrated that perindopril is effective against MPTP-induced neurodegeneration of the nigro-striatal dopaminergic pathway.
• The results suggest that free radical scavengers may be effective in the treatment of neurodegenerative diseases such as Parkinson disease.

Statistics:

• 1-methyl-4-phenyl-1,2,3,6-tetrahyropyrine (MPTP) was used in the study to induce Parkinson disease-like symptoms in mice.
• Perindopril was administered in doses of 0.01, 0.1, and 1 mg/kg to mice after MPTP treatment.
• Immunohistochemical studies were conducted with various antibodies, including tyrosine hydroxylase (TH), microtubule-associated protein 2a,b (MAP2), dopamine transporter (DAT), parvalbumin (PV), glial fibrillary acidic protein (GFAP), and Cu/Zn-superoxide dismutase (Cu/Zn-SOD).

Sources:

• R. Kurosaki et al., "Neuroprotective effect of the angiotensin-converting enzyme inhibitor perindopril in MPTP-treated mice. Neurol Res, 2004;26(6):644-657"
• University of Tokushima, Graduate School, Department of Drug Metabolism and Therapeutics, 1-78 Sho Machi, Tokushima 7708505, Japan
• Maney Publishing, Hudson Rd., Leeds LS9 7DL, England (publisher of Neurological Research journal)
• Proteomics Weekly editors, staff, and reports (prepared article)