Excess cholesterol could lead to negatively altered receptor functioning in brain cells, implicated in Alzheimer’s disease

By Kanika Kamal 

New research by the Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra has demonstrated the potentially negative effects of cholesterol on important proteins and receptors in the brain. Specifically, the research was built off of previous studies that found that cholesterol in brain cell membranes can negatively interfere with the function of the Adenosine Receptor of brain cells. The Adenosine Receptor is a type of G Protein-Coupled Receptor (GPCR) that is very important for signal transduction and cell-to-cell communication, especially between brain cells. Because of their important function, the Adenosine Receptors are aptly located in the cell membranes. These receptors are involved in several crucial physiological processes, such as in allowing vision, taste, and smell, in regulating the immune response, and in modulating behavior.

 In diseases such as Alzheimer’s, a neurodegenerative disease, there are increased levels of cholesterol in the cell membrane. This cholesterol can thus directly affect the function of the Adenosine Receptor and other GPCRs. Originally, it was thought that cholesterol changes the protein’s activity by either changing properties of the cell membrane itself or by binding to the surface of the protein. These new findings, however, have demonstrated that cholesterol from the brain cell membranes actually binds to the Adenosine Receptor’s active site. This discovery has lead scientists to further understand the direct effect that high cholesterol levels in diseases like Alzheimer’s have in blocking the Adenosine Receptor’s important function. They believe the blockage of the receptor could be directly related to the disease symptoms exhibited by patients.

Although the exact mechanism through which the cholesterol affects the Adenosine Receptor’s activity is unknown, this finding opens new pathways for investigation. As this discovery is quite new, further research is needed to prove this relationship. With this new knowledge, however, scientists could develop molecules similar to cholesterol and use them to modulate GPCR activity. Thus, the next logical research step is to see whether cholesterol only affects Adenosine Receptors, or whether this molecular mechanism can affect other GPCRs as well. If so, these findings could be a huge step forward in understanding the mechanism and developing treatments for a wider range of neurodegenerative diseases.

 

IMIM (Hospital del Mar Medical Research Institute). "New role of cholesterol in regulating brain proteins discovered: May be key in central nervous system diseases such as Alzheimer's." ScienceDaily. ScienceDaily, 23 February 2017. <www.sciencedaily.com/releases/2017/02/170223114836.htm>.