Although the cause of PD is unknown, pathological analyses have suggested the involvement of oxidative stress and mitochondrial dysfunction. Recently, an inherited form of early-onset PD has been linked to mutations in both copies of the gene encoding the mitochondrial protein PINK1. Furthermore, increasing evidence indicates that single-copy mutations in PINK1 are a significant risk factor in the development of later-onset PD.

In a study published this week in the open access journal PLoS Biology, Julia Pridgeon, Lian Li, and colleagues at Emory University show that PINK1 is a protein kinase that phosphorylates the mitochondrial molecular chaperone TRAP1 to promote cell survival. The researchers find that PINK1 normally protects against oxidative-stress-induced cell death by suppressing cytochrome c release from mitochondria. The PINK1 mutations linked to PD impair the ability of PINK1 to phosphorylate TRAP1 and promote cell survival. These findings reveal a novel anti-apoptotic signaling pathway that is disrupted by mutations in PINK1. This study suggests that this pathway has a role in PD pathogenesis and may be a target for therapeutic intervention.

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Dr Ulf Bergstr'm from the Malm' University Hospital, Sweden, lead investigator on both studies said, "The determinants for developing RA in any population are clearly complex and often unrelated. These studies help us to add more pieces to the giant jigsaw of risk factors for one of the most common autoimmune diseases, affecting approximately 1% of adults worldwide. We hope these findings will contribute to better understanding of future RA prevention and treatment. Whilst the glucose tolerance findings contrast with previous studies linking impaired tolerance to established RA, they suggest that other mechanisms may be important years before RA onset. Our results will pave the way for future debate and research to pinpoint its definitive causes."

The two studies involved people enrolled in the Malm' Diet and Cancer Study (MDCS) (n=30,447) between 1991 and 1996 and a Preventive Medicine Program (PMP) (n=33,346) between 1974 and 1992. Investigators examined lifestyle factors using a self-administered questionnaire and glucose tolerance and lipids readings were taken by health professionals. Individuals who developed RA after participation in the health surveys were compared to controls without RA from the PMP and MDCS, matched for age, sex and year of screening.

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