NURR1 and its transcriptional targets are downregulated in midbrain dopamine neurons that express high levels of the disease-causing protein α-synuclein, as observed in rodent models and patients with Parkinson diseaseα-Synuclein overexpression results in an almost complete blockade of GDNF trophic signalling and failure of GDNF to protect against α-synuclein-induced toxicity in affected neuronsReduced NURR1 expression might result in induction of dopamine neuron dysfunction as well progression of degenerative changes, which could make this protein a promising therapeutic target
activated. In particular, the team found that the naturally occurring molecule 5,6-dihydroxyindole (DHI), a dopamine metabolite, binds directly to and modulates the activity of Nurr1.
supposedly there is a clinical trial of lithium with regard to Nurr 1 which is not recruiting and there appear to be no results beta.clinicaltrials.gov/stu...
I take 132 mg or more per night after having done a year at 90+ mg/day and a year at 120+ mg/day, but I don't have PD, so I can't say how it would affect that. I am taking it for all of the health benefits that it has shown in studies.
The biological effects of melatonin regarding PD are vastly widespread. Studies have demonstrated its neuroprotective effects in improving both motor and non-motor impairments experienced by PD patients (Medeiros et al., 2007). Melatonin alleviated oxidative stress involved in neurodegeneration possibly via increasing SOD, CAT, GPx, and through decreasing MDA and dopaminergic neuronal death in the SN of a rat model of PD (Ozsoy et al., 2015). Administration of melatonin was premised on the inhibition of autophagic-induced neuronal cell death and neurotoxicity in PD (Su et al., 2015). Similarly, neuroinflammation reported in PD caused by the cyclooxygenase type 2 pathway was decreased by melatonin (Ortiz et al., 2013). Pathologically, this supplement decreased the a-synuclein levels in the striatum in monkey models of PD and also protected against dopamine loss in the substantia nigra, and further replenished the striatal dopamine loss (Paul et al., 2018). Genetically, mutations of the leucine-rich repeat kinase 2 (LRRK2) gene associated with sleep disorders and PD were significantly decreased when melatonin was administered (Sun et al., 2016).
I've used multiple sizes of capsules but am currently using 12 mg dissolvable tabs. For people who go for higher dosing such as the 180 mg~360 mg dosing recommended by Dr. Shallenberger, it is available in 60 mg capsules, making it much easier to take those higher dose ranges. Here is a typical one :
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What could be the cause of restless leg syndrome
Too much C/L
Recording available for NSB4PD webinar with Dr. Sackner-Bernstein on "Why I am optimistic that we might now have a Silver Bullet for PD"
