Dopamine Neuron Stimulating Peptides
Parkinson’s disease (PD) is a disabling neurodegenerative disorder, most often diagnosed in people over the age of 50, characterized by one or more of the following parkinsonian symptoms: bradykinesia, stooped posture, rigidity, resting hand tremors, balance impairments and gait difficulty. These multisymptoms are linked with the dysregulation of the neurotransmitter dopamine resulting from the loss of dopamine neurons. Glial cell line-derived neurotrophic factor (GDNF), a neurotrophic factor with protective and restorative effects on dopamine neurons in vitro and in vivo, was identified as a potential therapeutic agent for PD. However, GDNF did not progress from PD clinical trials, likely due to the pharmacological disadvantages associated with the invasive delivery of large protein molecules directly to the brain. We are examining the protective properties of dopamine neuron stimulating peptide-11 (DNSP-11, < 1/25th the size of GDNF) using a variety of different neurobiological approaches.
Selected Publications
Gash DM, Gerhardt GA, Bradley LH, Wagner R, Slevin JT. (2020) GDNF clinical trials for Parkinson's disease: a critical human dimension. Cell Tissue Res 382(1):65-70. DOI: 10.1007/s00441-020-03269-8.
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Stenslik MJ, Evans A, Pomerleau F, Weeks R, Huettl P, Foreman E, Turchan-Cholewo J, Andersen A, Cass WA, Zhang Z, Grondin RC, Gash DM, Gerhardt GA, Bradley LH. (2018) J Neuroscience Methods 303, 30-40.
DOI: 10.1016/j.jneumeth.2018.03.006
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Stenslik MJ, Potts LF, Sonne JWH, Cass WA, Turchan-Cholewo J, Pomerleau F, Huettl P, Gash DM, Gerhardt GA, Bradley LH. (2015) Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson’s disease. J Neuroscience Methods 251, 120-129. http://dx.doi.org/10.1016/j.jneumeth.2015.05.006.
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Fuqua JL, Littrell OM, Lundblad M, Turchan-Cholewo J, Abdelmoti LG, Galperin E, Bradley LH, Cass WA, Gash DM, Gerhardt GA. (2014) Dynamic Changes in the Dopamine Neuron Function after DNSP-11 Treatment: Effects in vivo and Increased ERK 1/2 Phosphorylation in vitro. Peptides 54: 1-8. http://dx.doi.org/10.1016/j.peptides.2013.12.007.
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Littrell OM, Fuqua JF, Richardson AD, Turchan-Cholewo J, Hascup ER, Huettl P, Pomerleau F, Bradley LH, Gash DM, Gerhardt GA. (2013) A synthetic five amino acid GDNF propeptide increases dopamine neuron differentiation and neurochemical function. Neuropeptides 47: 43-49. http://dx.doi.org/10.1016/j.npep.2012.08.004
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Kelps KA, Turchan-Cholewo J, Hascup ER, Taylor TL, Gash DM, Gerhardt GA, Bradley LH. (2011) Evaluation of the physical and in vitro protective activity of three synthetic peptides derived from the pro- and mature GDNF sequence. Neuropeptides 45(3): 213-218.
http://dx.doi.org/10.1016/j.npep.2011.03.003
Bradley LH, Fuqua J, Richardson A, Kelps KA, Ai Y, Turchan-Cholewo J, Glass J, He X, Zhang Z, Grondin R, Littrell OM, Gash DM, Gerhardt GA. (2010) Dopamine neuron stimulating actions of a GDNF propeptide. PLoS ONE 5(3): e9752. http://dx.doi.org/10.1371/journal.pone.0009752