TP10-dopamine conjugate as a potential therapeutic agent in the treatment of Parkinson’s disease
Izabela Rusiecka , Jarosław Ruczyński , Agnieszka Kozłowska , Ewelina Backtrog , Piotr Mucha , Ivan Kocić , Piotr Rekowski
AbstractParkinson’s disease (PD) is a common progressive neurodegenerative disorder for which the current treatment is not fully satisfactory. One of the major drawbacks of current PD therapy is poor penetration of drugs across the blood-brain barrier (BBB). In recent years, cell-penetrating peptides (CPPs) such as Tat, SynB, or TP10 have gained great interest due to their ability to penetrate cell membranes and to deliver different cargos to their targets including the central nervous system (CNS). However, there is no data with respect to the use of CPPs as drug carriers to the brain for the treatment of PD. In the presented research, the covalent TP10-dopamine conjugate was synthesized and its pharmacological properties were characterized in terms of its ability to penetrate the BBB and anti-parkinsonian activity. The results showed that dopamine (DA) in the form of a conjugate with TP10 evidently gained access to the brain tissue, exhibited low susceptibility to O-methylation reaction by catechol-O-methyltransferase (lower than that of DA), possessed a relatively high affinity to both dopamine D1 and D2 receptors (in the case of D1, a much higher than that of DA), and showed antiparkinsonian activity (higher than that of L-DOPA) in the MPTP-induced preclinical animal model of PD. The presented results prove that the conjugation of TP10 with DA may be a good starting point for the development of a new strategy for the treatment of PD.
|Journal series||Bioconjugate Chemistry, ISSN 1043-1802, (A 35 pkt)|
|Publication size in sheets||0.7|
|Keywords in Polish||transportan 10, dopamina, choroba Parkinsona, bariera krew-mózg, chemia klik|
|Score|| = 35.0, 03-03-2019, ArticleFromJournal|
= 40.0, 03-03-2019, ArticleFromJournal
|Publication indicators||: 2017 = 4.485 (2) - 2017=4.416 (5)|
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