Supporting Parkinson's Disease Research, Education, Patients and Caregivers.
Parkinson Discovery Institute
Parkinson's disease is the second most common neurodegenerative disease, affecting ~ one million people in the US alone. It is a disease strongly associated with aging and is progressive. It not only impairs the ability to initiate and maintain movement, it also is marked by tremor at rest and rigidity in gait. As a result, balance is often compromised as the disease progresses. We do not know what causes the majority (~90%) of cases, and presently there are no disease modifying therapies. However, it is becoming evident that regular practice of aerobic exercise can slow the rate of progression. When we identify the key mechanisms the drive the loss of the dopamine neurons that are affected by this disease, we will begin to disentangle exactly how exercise mitigates the impact of disease mechanisms. This will identify critical brain proteins to target for therapy.
Growth factor signaling plays a critical role in the maintenance of dopamine neurons. During disease progression, the receptor (GFRa1) for one growth factor called GDNF is decreases in expression. This loss is directly tied to the expression of the key protein responsible for dopamine synthesis, called tyrosine hydroxylase (TH). Here in this image from our labs published study in Experimental Neurology, we show the progressive loss of GFRa1 is directly linked to TH protein expression. From Kasanga et al., 2023.
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Kasanga, E.A., Soto, I., Centner, A., McManus, R., Shifflet, M.K., Navarrete, W., Han, Y., Lisk, J., Ehrhardt, T., Wheeler, K., Mhatre-Winters, I., Richardson, J.R., Bishop, C., Nejtek, V.A., Salvatore, M.F. Moderate intensity aerobic exercise alleviates motor deficits in 6-OHDA lesioned rats and reduces serum levels of biomarkers of Parkinson's disease severity without recovery of striatal dopamine or tyrosine hydroxylase. Exp Neurol 379: 114875, 2024.
Soto, I., Nejtek, V.A., Siderovski, D.P., Salvatore, M.F. PINK1 knockout rats show premotor cognitive deficits measured through a complex maze. Front Neurosci 18: 1390215, 2024.
Soto, I., McManus, R., Navarrete, W., Kasanga, E.A., Doshier, K., Nejtek, V.A., Salvatore, M.F. Aging accelerates locomotor decline in PINK1 knockout rats in association with decreased nigral, but not striatal, dopamine and tyrosine hydroxylase expression. Exp Neurol 376, 114771, 2024. PMID 38580154
Salvatore, M.F. Dopamine signaling in substantia nigra and its impact on locomotor function; not a new concept, but neglected reality. Int J Mol Sci 25: 1131, 2024. PMID 38256204
Kasanga, E.A. Han, Y., Shifflet, M.K., Navarrete, W., McManus, R., Parry, C., Barahona, A., Nejtek, V.A., Manfredsson, F.P., Kordower, J.H., Richardson, Salvatore, M.F. Nigral-specific increase in ser31 phosphorylation compensates for tyrosine hydroxylase protein and nigrostriatal neuron loss: Implications for delaying parkinsonian signs. Exp Neurol 368: 114509, 2023. PMID 37634696
Kasanga, E.A., Han, Y., Navarrete, W., McManus, R., Shifflet, M.K., Parry, C., Barahona, A., Manfredsson, F.P., Nejtek, V.A., Richardson, J.R., Salvatore, M.F. Differential expression of RET and GDNF family receptor, GFR-a1, between striatum and substantia nigra following nigrostriatal lesion: a case for diminished GDNF signaling. Exp Neurol. 366: 114435, 2023. PMID 37178997
Salvatore, M.F., Soto, I., Kasanga, E.A., James, R., Shifflet, M.K., Doshier, K., Little, J.T., John, J., Alphonso, H.M., Cunningham, J.T., Nejtek, V.A. Establishing equivalent aerobic exercise parameters between early-stage Parkinson's disease and Pink1 knockout rats. J Parkinson's Dis. 12: 1897-1915, 2022. PMID 35754287
Salvatore, M.F., Kasanga, E.A., Kelly,P., Venable, K.E. Cantu, M.A., McInnis T.R., Terrebonne, J., Lanza, K., Meadows, S.M., Centner, A., Bishop, C., Ingram, D.K. Modulation of nigral dopamine signaling mitigates parkinsonian signs of aging: evidence from intervention with calorie restriction or inhibition of dopamine uptake. GeroScience. 45: 45-63, 2023 PMID 35635679
Kasanga, E.A., Little J., McInnis, T.R., Bugnariu, N., Cunningham, J.T., Salvatore, M.F. Cardiovascular Metrics Associated With Prevention of Aging-Related Parkinsonian Signs Following Exercise Intervention in Sedentary Older Rats. Front Aging Neurosci 13:775355, 2021. PMID 34975456.
Nejtek, V.A., James, R.N., Salvatore, M.F., Alphonso, H.M., Boehm, G.W. Premature cognitive decline in specific domains found in young veterans with mTBI coincide with elder normative scores and advanced-age subjects with early-stage Parkinson’s disease. PLoS ONE 16(11):e0258851, 2021. PMID 34788310.
Salvatore, M.F., Soto, I., Alphonso, H., Cunningham, R., James, R., Nejtek, V.A. Is there a neurobiological rationale for the utility of the Iowa Gambling Task in Parkinson’s Disease? J Parkinson’s Dis. 11(2): 405-419, 2021. PMID 33361612.
About Us
Our Mission
The Parkinson Discovery Institute is dedicated to advancing research and knowledge to patients and their families about Parkinson's disease. We are committed to the conduct of innovative projects and initiatives that aim to improve the quality of life for individuals affected by Parkinson's. Our research focuses on the critical importance of translational research. Our outreach focuses on bringing the patient and their caregivers the latest research and medical care from our work, our collaborators, and dedicated researchers and practitioners in neurodegenerative disease and aging. Our focus is to be a major contributor in driving progress in treatment options and care practices.
Our Initiatives
Research
Our research projects focus on the mechanistic basis of the beneficial impact of exercise on patients battling Parkinson's disease. This includes enhancing diagnostic methods as early as possible in the disease stage and ascertaining the efficacy of exercise. Being at the forefront of this endeavor, we aim to make significant strides in the field of Parkinson's research that translate to the patient.
Awareness
Raising awareness about the challenges with a Parkinson's disease diagnosis is crucial. This includes lifestyles we can employ in our daily life to reduce risk. Our quarterly awareness campaigns aim to educate and empower patients and their caregivers in their knowledge of treatments, learn ways to overcome challenges of the disease, and see the progress in Parkinson's research.
Support
Based on recent studies, there are an estimated 28,000 individuals and families in the DFW Metroplex that deal with Parkinson's on a daily basis. Since Parkinson's is a disease strongly associated with aging, this need will increase as we age as a population. The PDI aims to provide essential support services and resources for individuals living with Parkinson's and their families.