I believe this is worth a try. However, as a former believer and user (wife) of low dose naltrexone, I can also be skeptical of many of these ncbi/nih papers. But, combined with good doses of curcumin and VD3, mannitol is worth a try for a year.



A Blood-Brain Barrier (BBB) Disrupter Is Also a Potent α-Synuclein (α-syn) Aggregation Inhibitor

Mannitol also exhibited specific neuroprotective qualities in the dopaminergic system of the treated mice, where it was able to restore TH immunoreactivity in the mThy1-α-syn tg mice back to levels comparable with vehicle-treated non-tg mice in the BG. Importantly, mannitol had no general neuroprotective effect on the control non-tg mice.
Mannitol seems to have a preventive ability to inhibit α-syn aggregation, but not a reversive ability. Mannitol was not able to dissolve preformed α-syn aggregates in vitro nor to dissolve α-syn aggregates when dripped on brain sections taken from α-syn tg mice.
Abnormal protein misfolding and aggregation are key features in many neurodegenerative disorders. Interestingly, a decline in the intracellular level of molecular chaperones was shown to increase the levels of abnormally folded proteins inside the cell (39). Therefore, it was proposed that the cell toxicity in neurodegenerative disorders may result from an imbalance between normal chaperone capacity and the production of misfolded protein species (40). Hence, the addition of chemical and molecular chaperones, which are able to stabilize misfolded proteins, was suggested as a therapeutic approach in neurodegenerative disorders (22). In addition to its BBB-disrupting properties, mannitol was previously suggested to function as a chemical chaperone, demonstrating a very potent effect on the stabilization of protein structure (19–21).
Here, we have demonstrated that mannitol interferes with α-syn aggregation in vitro and in vivo, whereas no adverse effects were observed in control-treated flies or mice. In addition to its osmotic diuretic effect, mannitol is known for its BBB-disrupting properties (41). To the best of our knowledge, mannitol has not been tested or used until now in the clinic for drug delivery into the brain. Therefore, we suggest that mannitol administration in combination with other drugs could be a promising new approach for treating PD and other brain-related diseases such as Alzheimer disease. This prediction is based on its chemical chaperone properties, its vast protective cellular capabilities, and its BBB-disrupting properties.