Identifying Specific Neural Markers Can Assist in the Development of Therapeutics

The genetic makeup that an individual possesses plays a significant role in determining their susceptibility to cognitive aging and neurodegeneration. Many humans fall prisoner to neurodegenerative diseases such as Alzheimers, Parkinson's, and Hutchinson-Gilford Progeria syndrome. Identifying specific genes that contribute to cognitive decline in these diseases, and in general, can aid in early diagnosis and even serve as targets for therapeutics. Identifying specific genetic markers could be challenging because the ability to do so involves complex genetics, limited access to human subjects, and difficulty controlling environmental factors. 

In the article, “Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging,” Catherine C. Kaczorowski et al. conduct experiments to identify specific genes and proteins that play a part in cognitive aging. Aging or neurodegeneration is associated with a decline in cognitive performance that begins around the age of 45 to 50 years old. The severity of this decline, however, varies amongst individuals. Researchers from the study used BXDs, a type of genetic reference panel, that allowed them to exploit phenotypic heterogeneity across a population while concurrently controlling for environmental factors. Catherine C. Kaczorowski et al. successfully used BXDs to identify genomic regions that are important for learning and memory. Identifying these specific genes or proteins that modify the development of cognitive decline can aid in early diagnosis of patients. Furthermore, their identification can assist in recognition of  therapeutic targets to treat or prevent symptoms. In the text, researchers state, “we identify Hp1bp3 as a novel modulator of cognitive aging using a genetically diverse population of mice, and confirm that HP1BP3 protein levels significantly reduced in the hippocampi of cognitively impaured elderly humans relative to intact controls'' (Catherine C. Kaczorowski et al. 1). Dr. Kaczorowski’s team concluded that the deletion of the Hp1bp3 protein resulted in memory deficits corresponding with aged mice and humans. This led them to believe that Hp1bp3 and molecular networks are modulators of cognitive control. The researchers used genetic reference panels, specifically BXDs, to exploit phenotypic heterogeneity across a population and determined that Hp1bp3 played a vital role as the novel modulator in cognitive aging. 

Cognitive aging can also be seen in Hutchinson-Gilford Progeria syndrome or the “Benjamin Button” disease. Progeria is a rare genetic condition in which a child’s body ages at rapid speeds. In the research article, “An overview of treatment strategies for Hutchinson-Gilford Progeria syndrome,” Karim Harihouri et al. explain that Progeria is an autosomal dominant disorder that accelerates aging and leads to the death of children around the time they turn 14. Scientists have discovered that this disease is caused by a mutation in the LMNA gene. In the text, researchers state, “This mutation leads to the production of a truncated toxic form of lamin A, issued from aberrant splicing and called progerin. Progerin accumulates in HGPS cells’ nuclei and is a hallmark of the disease” (Karim Harihouri et al. 1). From this, we can conclude that the mutation in the LMNA gene is the leading factor in the development of Progeria. 

In both articles, cognitive decline is correlated with the appearance or the mutation of a specific protein or gene. Although age related cognitive decline is inevitable, the ability to associate cognitive decline with specific genes or proteins could lead to the development of therapeutics that assist in slowing down the aging process. The Benjamin Button disease has no cure but researchers are working on finding one. Some doctors suggest certain drugs and changes in diet to lower cholesterol and prevent blood clots. Both Dr. Kaczorowski and Karim Harihouri’s research teams identify specific genes or proteins that are associated with cognitive aging or neurodegenerative disease. Aging is a part of life and everyone does it. However, sometimes cognitive aging occurs at drastic rates or sooner than it should. In cases such as these, it's important that we have the ability to control and prevent it. Identifying genetic markers associated with particular diseases opens the door to several opportunities for therapeutics that bring us one step closer to understanding the true nature of an illness. By understanding an illness, one can cure or prevent it. 

References 

Harhouri, Karim, et al. “An Overview of Treatment Strategies for Hutchinson-Gilford Progeria Syndrome.” Taylor & Francis, 2018, www.tandfonline.com/doi/full/10.1080/19491034.2018.1460045. 

Nazario, Brunilda. “Progeria: Causes, Symptoms, and Treatments.” WebMD, WebMD, 8 Sept. 2020, www.webmd.com/children/progeria. 

Neuner, Sarah M., et al. “Systems Genetics Identifies Hp1bp3 as a Novel Modulator of Cognitive                      Aging.” Neurobiology of Aging, vol. 46, 2016, pp. 58–67.,    doi:10.1016/j.neurobiolaging.2016.06.008.