A picture of Parkison's Disease
Image of Lewy bodies (brown), a histological feature of Parkinson’s disease made up of alpha-synuclein. Photograph courtesy of Lary C. Walker, Ph.D., Emory University School of Medicine

Sniffing Out Parkinson's Disease

Study Finds Parkinson's Disease May Arise From Immune Molecule

It’s a curious fact that Parkinson’s disease — a condition characterized by the inability to initiate or control movements — often begins with the inability to detect odors. Ning Quan, Ph.D., professor of biomedical science in the Charles E. Schmidt College of Science, said he thinks the basis for this loss may lie with molecules that communicate inflammation to the brain.

Years ago, researchers uncovered the fact that Parkinson’s disease (PD) in some patients arises from a genetic mutation that produces a toxic form of the protein alpha-synuclein. Mutant alpha-synuclein proteins clump up in tangles that can travel to areas of the brain that produce dopamine, a chemical that neurons use to regulate movement and motivation. There the toxic alpha synuclein proteins kill the dopamine-producing neurons, the basis for the disease.

But only a few Parkinson’s patients inherit a mutated alpha-synuclein gene. Haichen Niu, Ph.D., a collaborator of Quan’s, who runs a lab at the Xuzhou Medical College in China, wondered how these individuals acquire PD. Noting that the disorder can begin with an inability to smell, Niu hypothesized that the entire process could be kicked off by inhaling something toxic —maybe a virus, maybe an allergen, maybe air pollution — which inflames brain olfactory neurons. Niu reasoned that this inflammation might stimulate the production and clumping of alpha-synuclein, which might then travel to the area of the brain where dopamine neurons are located and kill them, resulting in PD.

To test his hypothesis, Quan said Niu and his team nasally administered a fever-inducing molecule to mice, then examined changes in their brains six weeks later. The studies revealed that nasal inflammation activated the production of an immune molecule, called interleukin-1, which caused the alpha-synuclein to clump. These clumps were also found to have traveled to the dopamine-producing area of the brain, killing the dopamine neurons. These findings suggest that nasal inflammation may contribute to loss of a sense of smell in Parkinson’s patients and, more importantly, play an important role in damaging the dopamine neurons that produce Parkinson’s disease.

“If interleukin-1 plays a role, then it’s not unreasonable to think that in the future, we may be able to prevent the development of Parkinson’s disease if detected in its earliest stages by giving patients a drug like Anakinra, which blocks the actions of interleukin-1, and which is already FDA- approved for the treatment of juvenile arthritis,” said Quan, a co-investigator on Niu’s recently published study in Brain Pathology.

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