Objective: One candidate is CR6-interacting factor1 (CRIF1), which controls translation and membrane insertion of 13 mitochondrial proteins involved in oxidative phosphorylation. Here we determined the change and impact of CRIF1 for PD progression with human postmortem brains and mice.

Background: Mitochondrial dysfunction has been implicated in Parkinson’s Disease (PD) progression; however, the mitochondrial factors underlying the development of PD symptoms remain unclear.

Methods: We assessed the change of CRIF1 expression using real time PCR, western blotting and immunohistochemistry in postmortem brains. And to evaluate the effect of Crif1 deficiency, we produced mice lacking the Crif1 gene in dopaminergic neurons (DAT-CRIF1-KO mice). Behavioral and biochemical changes studied with DAT-CRIF1-KO mice whether represent the human PD symptoms or not.

Results: We found that CRIF1 mRNA and protein expression were significantly reduced in postmortem brains of elderly PD patients compared to normal controls. DAT-CRIF1-KO mice began to show decreased dopamine production with progressive neuronal degeneration in the nigral area from 5 weeks of age. At ~10 weeks of age, they developed PD-like behavioral deficits, including gait abnormalities, rigidity, and resting tremor. L-DOPA, a medication used to treat PD, ameliorated these defects at an early stage, but induced stereotypic motor abnormalities in older animals.

Conclusions: These findings that down-regulation of Crif1 promotes the progression of PD could potentially form the basis of therapeutic approach through on the up-regulation of Crif1-associated functions in PD patients.

References: Kim, S. J., et al. (2012). “CRIF1 is essential for the synthesis and insertion of oxidative phosphorylation polypeptides in the mammalian mitochondrial membrane.” Cell Metab 16(2): 274-283.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cr6-interacting-factor1-deficiency-in-dopamine-neurons-triggers-early-onset-parkinsonism-in-mice/