Microglia inflammation and autophagy play important roles in the initiation and progression of Parkinson’s disease (PD). Toll-like receptor 2 (TLR2) activation is closely related to microglial activation and enhances the cell-to-cell propagation of a-synuclein pathology. Clinical and preclinical samples also observed the impaired autophagy-lysosomal systems. As such, therapeutic strategies that inhibit TLR2 and/or modulate autophagy may be effective for PD treatment. As an autophagy inducer, rapamycin is initially used in the treatment of a variety of tumors by inhibiting mTORC1. Recently, rapamycin was reported to exert the anti-inflammatory effects in a variety of inflammatory diseases. Here, we employed the rotenone-induced Parkinson’s disease mouse model and peptidoglycan (PGN) cultured BV-2 cells to investigate whether rapamycin (Rapa) can act on PD by influencing TLR2 activation in vitro and in vivo experiments. The autophagy flux and the expression of inflammation related pathways downstream of TLR2 were examined. Our results showed that rapamycin increased the expression of LC3β to clear the accumulation of α-synuclein S129 phosphorylated(P-α-syn) and improved motor dysfunction in rotenone-induced PD mice, moreover, rapamycin inhibited the expression of TLR2 in microglia, further reduced nuclear translocation of nuclear factor of activated T cells, cytoplasmic 2(NFATc2) and downregulated gene expression of tumor necrosis factor-α (TNF-α) in vitro and in vivo. These results demonstrate that rapamycin exerts therapeutic effects via enhancing autophagy and suppressing the expression of TLR2 in rotenone-induced PD mice.
mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis
I don’t know if age-related “essential tremors” share any of the same mechanisms of Parkinson’s but tremors are certainly very common in Parkinson’s. Before I started rapamycin I had developed tremors in my hands that were starting to make it difficult to eat.
After about three months of taking rapamycin, I noticed that my tremors were completely gone and my hands are as steady as they were when I was young. I know that this is just an N=1 result, but I don’t know what else other than rapamycin I can attribute it to.
Late reply but just commented in another thread about the dopaminergic neuron loss that causes parkinson’s also happening in “healthy” aging just to a lesser extent. A lot of the cognitive and motor skill losses in older age can be attributed to dopaminergic neuron loss. The rate is about 5-10% per decade.
I haven’t looked into it much yet but I believe Dr Knoll produced an ebook delineating how Selegiline may be protective for dopaminergic neurons. This was discussed on this site in one of the threads about Selegiline. The ebook was linked in one those threads as well.
