Gemfibrozil Protects Dopaminergic Neurons in a MouseModel of Parkinson’s Disease via PPARa-DependentAstrocytic GDNF Pathway 2021

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Gemfibrozil Protects Dopaminergic Neurons in a MouseModel of Parkinson’s Disease via PPARa-DependentAstrocytic GDNF Pathway 2021 jneurosci.org/content/jneur...

"Parkinson’s disease (PD) is the most common neurodegenerative movement disorder in humans. Despite intense investigations, effective therapies are not yet available to halt the progression of PD. Gemfibrozil, a Food and Drug Administration-approved lipid-lowering drug, is known to decrease the risk of coronary heart disease by increasing the level of high-density lipoprotein cholesterol and decreasing the level of low-density lipoprotein cholesterol. This study underlines the importance of gemfibrozil in protecting dopaminergic neurons in an animal model of PD. Oral administration of the human equivalent dose of gemfibrozil protected tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta and TH fibers in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-insulted mice of both sexes.

Accordingly, gemfibrozil also normalized striatal neurotransmitters and improved locomotor activities in MPTP-intoxicated mice. Gemfibrozil-mediated protection of the nigrostriatal and locomotor activities in WT but not PPARa2/2 mice from MPTP intoxication suggests that gemfibrozil needs the involvement of peroxisome proliferator-activated receptor a (PPARa) in protecting dopaminergic neurons. While investigating further mechanisms, we found that gemfibrozil stimulated the tran-scription of glial-derived neurotrophic factor (GDNF) gene in astrocytes via PPARa and that gemfibrozil protected nigral neu-rons, normalized striatal fibers and neurotransmitters, and improved locomotor activities in MPTP-intoxicated Gfaf cre mice, but not Gdnf Dastro mice lacking GDNF in astrocytes. These findings highlight the importance of the PPARa-dependent astro-glial GDNF pathway in gemfibrozil-mediated protection of dopaminergic neurons in an animal model of PD and suggest the possible therapeutic use of gemfibrozil in PD patients."

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They trialed this for AD but have not posted results: clinicaltrials.gov/ct2/show...

[park_bear]

They applied the test substance four hours after treatment with toxicant. Wish they had waited longer but this is certainly better than pretreatment.

"Gemfibrozil treatment. Gemfibrozil was solubilized in 0.5% methyl

cellulose, and mice were treated with gemfibrozil once daily at a dose of

7.5 mg/kg in a volume of 50 ml via gavage starting from 4 h after the last

injection of MPTP. We adopted the time frame to avoid any effect of

gemfibrozil on the metabolism of MPTP in the brain"

A lot of adverse effects for this kind of medication:

drugs.com/sfx/gemfibrozil-s...