Mechanisms of Olfactory Deficits in Parkinson s Disease
Abstract
Most Parkinson’s disease patients lose their sense of smell, sometimes decades before they develop the symptoms typically associated with the disease, such as tremors and difficulty walking. Olfactory deficits, hyposmia or anosmia, is now recognized as a feature of early Parkinson’s disease and an indication that the disease is progressing insidiously. In this Fiscal Year 2016 Parkinson’s Research Program Focused Idea Award application, we will examine the underlying causes for olfactory deficits seen in Parkinson’s patients. The focus of our application is directly in line with the Focus Area of “Identification and evaluation of mechanisms in early Parkinson’s disease involving olfactory, microbiome, gastrointestinal, and/or autonomic nervous systems.” In this grant, we will examine how a protein known as alpha-synuclein, which forms abnormal deposits that are a signature of Parkinson’s disease, impacts nerve connections or synapses in the olfactory system. We suggest that in Parkinson’s disease, due to the presence of these abnormal alpha-synuclein deposits, both the structure and function of olfactory nerve connections are not proper. We will examine this question through our complementary expertise in the olfactory system and alpha-synuclein biology, using high resolution microscopic methods on mouse models that express mutant forms of alpha-synuclein that are linked to the disease. When we have successfully finished this study, we anticipate having a detailed picture of the synaptic abnormalities in the olfactory system in an animal model of early Parkinson’s disease. This will allow us to treat the loss of smell in early Parkinson’s disease patients in 5-10 years. But more importantly, as the nose and the olfactory system are thought to be a conduit through which alpha-synuclein deposits spreads, eventually reaching the mid-brain, a greater understanding of this pathway will permit us to slow the progression or even prevent Parkinson’s disease. This is the ultimate goal of all Parkinson’s disease research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710564
Entities
People
- Sreeganga S Chandra
Organizations
- United States Army
- Yale University