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Mitochondrial dysfunction results in increased production of ROS which activates stress responses leading to increased activity of MAPK and JNK

In the 1980s, a pilot preclinical study on two rat and monkey PD models 16 and two independent clinical cases 17,18 showed that intracerebroventricular (i.c.v.) administration of dopamine improved motor symptoms, but also resulted in tachyphylaxia, possibly owing to dopamine oxidation despite the use of a preservative solution (sodium metabisulfite), precluding the therapeutic development of this concept

For retatrutide at clinical doses, GLP-1R provides the baseline incretin HR rise (23 bpm)

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doi: 10.1523/ENEURO.0162-17.2017 106 ChalkiadakiKStatoullaEZafeiriMVoudouriGAmvrosiadisTTypouAet al