Parkinson’s disease (PD) is a progressive disorder of the brain that slowly robs an individual of the ability to initiate voluntary movement, eventually leaving them totally frozen. The disease also has non-motor components including reduced GI motility, depression, and cognitive deficits. As many as 1 million Americans live with Parkinson's disease and approximately 50,000 Americans are diagnosed with PD each year. The average age of onset is 60, however, people as young as 18 have been diagnosed with PD. The combined direct and indirect cost of Parkinson’s, including treatment, social security payments and lost income from inability to work, is estimated to be nearly $25 billion per year in the United States alone. Thus, the ultimate goal of medical research is to improve and maintain quality of life in those suffering with this disease. The motor deficits of PD result from death of a specific population of nerve cells in a brain region called the substantia nigra. These cells manufacture the chemical transmitter dopamine, which is necessary for the initiation of voluntary motor movement. As dopamine is lost from cell death, symptoms of the disease emerge.
The gold standard for symptomatic treatment of the motor symptoms PD is levodopa (or Sinemet) which helps restore dopamine levels in the brain. While levodopa works well in many patients early in the disease, the efficacy wanes as the disease progresses and debilitating side-effects known as dyskinesias develop. Accordingly, new therapeutics and improved treatment strategies are desperately needed for both the motor and non-motor symptoms in order to improve the lives of those affected by the disease. Here in TSMM, our highest priority is developing new treatments to slow or halt the progression of PD, and to allow for sustained, symptomatic benefit. The TSMM PD team has been designated by the National Institutes of Health as one of ten Morris K. Udall Centers of Excellence in Parkinson’s disease and is a highly interknit team of Molecular Geneticists, Cell, Protein and Molecular Biologists, Biochemists, Neuroanatomists and Behavioral Scientists, all working toward the rapid development of new candidate therapies for PD.
Alzheimer's disease (AD) is the most common form of dementia (~50-80% of all dementias) and is characterized by a progressive loss of brain cells (i.e. neurons) in regions of the brain that are important for memory and cognition. AD is currently the 6th leading cause of death in the US, affecting over 5 million people 65 years of age and older. The costs to the healthcare system are estimated at over $180 billion annually in the US alone. The greatest risk factor for developing AD is increasing age with onset typically occurring in the 6th decade of life. The symptoms get progressively worse with time and typically include memory loss, confusion, difficulty completing familiar tasks, trouble understanding visual information, social withdrawal, and mood/personality changes. Both early-onset (prior to age 65) and genetic forms of AD exist, but account for a small percent of all AD cases.
The cause(s) of AD remain unclear, but much of the research focuses on cellular events that revolve around two important proteins, amyloid-beta and tau, which undergo abnormal changes in the affected areas of the brain. While the precise function of amyloid-beta is still uncertain, it appears to be important for proper neuron function and survival through multiple mechanisms. Tau protein is an important component of the structural framework of neurons and plays a role in multiple cellular processes (i.e. microtubule stability and intracellular transport). Within TSMM, investigations are focused on understanding the molecular mechanisms underlying neuron dysfunction and death in AD. Specifically, how changes in tau cause dysfunction in neurons and ultimately lead to neuron death.
Cognitive and neurological deficits associated with “natural” as well as pathological aging in the brain, including Alzheimer’s disease, Parkinson’s Disease, stroke, and atherosclerosis, affect an increasingly large portion of the population each year, costing millions of dollars in health care, lost productivity, and an under-appreciated emotional toll on family and loved ones. The Administration on Aging statistics collected in 2009 indicated that 39.6 million individuals were 65 years or older, representing 12.4% of the population of the United States. They project that as the Baby Boom Generation matures, this number will rise to 72.1 million individuals by the year 2030, representing 19% of the population, more than double the number of individuals in the year 2000.
Aging is acknowledged to be the primary risk factor for the most common neurodegenerative diseases. As such, the mechanisms of aging are a primary research focus of our team of investigators. Our goal is to identify factors that promote “successful aging”, allowing individuals to outlive the onset of these disorders.
The problem is complex. Aging is not a disease, it is a mosaic of changes in many systems of the brain, and body: inflammation, mishandling of damaged proteins, accumulation of oxidative stress, decline in growth-promoting chemicals, decreased repair of damaged DNA, and others.
Our work focuses on aging as a final common path for aging-related disorders. Interventions that are “anti-aging, may relieve the burden of these devastating disorders.