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A new $3.7 million federally funded study led by Dr. Robert Smith, professor and chair of the Department of Neurosciences and Psychiatry, is hoped to unlock new clues about the starting point and progression of Alzheimer\u2019s disease.<\/p><\/div>\n
Only three drugs have U.S. Food and Drug Administration approval for the disease, and both run the risk of serious side effects in return for modest cognitive improvements.<\/p>\n
\u201cAlzheimer\u2019s is a devastating disease and despite all the work that has been done, we still don\u2019t have a solid grasp of how it develops or how we can safely and effectively treat it,\u201d Smith said. \u201cClearly, we need a different approach.\u201d<\/p>\n
Smith recently was awarded a $3.7 million grant from the National Institute on Aging for a study that will analyze post-mortem brain samples from control individuals, individuals with mild cognitive impairment and individuals who received an Alzheimer\u2019s diagnosis prior to their death.<\/p>\n
Using cutting-edge tools, their lab will map out and compare the function of more than 500 individual kinase protein signaling pathways across those three subsets of brain tissue.<\/p>\n
The project, Smith said, differs from previous research on the disease in both what scientists are looking at and in what they\u2019re expecting to find.<\/p>\n
Most federally funded research projects are formed around a single hypothesis. The work, more or less, is trying to further prove or disprove that idea.<\/p>\n
UToledo researchers have no pre-set expectations.<\/p>\n
\u201cThis is a hypothesis-generating project,\u201d Smith said. \u201cWe have a lot of really good preliminary data and many potential targets, but we are coming at this with an open mind. Our study is completely agnostic to what everyone else is doing.\u201d<\/p>\n
UToledo\u2019s team also is using a different method to measure what\u2019s happening in the brain\u2019s complex signaling pathways than other studies have employed.<\/p>\n
Protein kinases, which are the enzymes Smith\u2019s team is studying, add phosphates to proteins, changing their activity and creating complex regulatory networks. They allow for essential processes, but many of the 500-plus protein kinases in the human body are poorly understood, let alone well-studied in the context of Alzheimer\u2019s disease.<\/p>\n
By employing something called a kinome array, researchers can measure how much work protein kinase are doing within the brain\u2019s signaling network, illuminating how its actions cascade through the brain.<\/p>\n
Much of the existing literature, Smith said, has come from studies that looked only at how much of a protein was present in the brain \u2014 not its activity level.<\/p>\n
\u201cYou can have no change in the amount of a protein with a big change in activity,\u201d Smith said. \u201cWe are looking at Alzheimer\u2019s in a way that it has never been looked at before, looking at parts of the genome that have never been looked at before. At the end of this study, we hope to have identified the cell types and the protein kinases that should be targeted for new drugs to block the progression of cognitive impairment seen in Alzheimer\u2019s dementia. This is a moonshot project.\u201d<\/p>\n
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