Alzheimer’s Disease: Repairing Golgi Structures May Reduce Toxic Plaques

Yanzhuang Wang, PhD Associate professor Dept. of Molecular, Cellular and Developmental Biology and Dept. of Neurology University of Michigan Ann Arbor, MI 48109-1048MedicalResearch.com Interview with:
Yanzhuang Wang, PhD
Associate professor
Dept. of Molecular, Cellular and Developmental Biology and Dept. of Neurology University of Michigan
Ann Arbor, MI 48109-1048

 MedicalResearch.com: What are the main findings of the study?

Dr. Wang: We learned how to repair a cellular structure called the Golgi apparatus that is broken in Alzheimer’s disease. This helps us understand how to reduce the formation of the toxic plaques that kill cells in the brain of Alzheimer’s patients. The formation of amyloid plaques is a hallmark of Alzheimer’s disease; but exactly how much the plaques contribute to the disease is still not known. Our study found that the broken Golgi in the disease may be a major source of the toxicity of amyloid plaques. We showed in this study that repairing the Golgi can reduce the formation of the toxic plaques and thus may delay the disease development.

MedicalResearch.com: Were any of the findings unexpected?

Dr. Wang: It is unexpected to see that amyloid plaques exert their toxicity by affecting the Golgi structure and function. The Golgi is a cellular organelle that functions like the post office in the cell. It sends proteins where they are supposed to go; many of these proteins need to go to the right places to perform cellular functions. When the Golgi malfunctions it’s like the post office stops sending mail or sends it to the wrong place. This can cause health problems. Because Golgi defects contribute to the formation of the toxic plaques in the brain, repairing the Golgi can reduce the formation of these plaques and missorting of proteins in the cell.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Wang: Alzheimer’s patients have these plaques, but exactly how they cause the disease is still not known. The finding of Golgi defects may help us understand the cause of the disease, and repairing the Golgi may reduce the formation of the toxic plaques. In this sense we have identified the Golgi as a new drug target for the treatment of the disease because molecular tool that can restore Golgi structure and function may delay disease development.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Wang: So far our idea is mainly based on experiments in cells in the petri dish. In the next a few years we will test this idea in mouse models and screen for small molecules that could potentially be used to repair the Golgi in the brain of Alzheimer’s patients. If our findings go well, we may be able to develop a potent drug to help slow the formation of these plaques and delay the disease development in patients in the future.

Citation:

Gunjan Joshi, Youjian Chi, Zheping Huang, and Yanzhuang Wang

Aβ-induced Golgi fragmentation in Alzheimer’s disease enhances Aβ production PNAS 2014 ; published ahead of print March 17, 2014, doi:10.1073/pnas.1320192111