dfwl28: Thanks for sharing. Very interesting.
Post# of 148155
Thanks for sharing. Very interesting. I paste below some excerpts from the paper published in Neuron:
SUMMARY
In neurodegenerative diseases, microglia switch to an activated state, which results in excessive secretion ofpro-inflammatory factors. Our work aims to investigate how this paracrine signaling affects neuronal function. Here, we show that activated microglia mediate non-cell-autonomous inhibition of neuronal autophagy, a degradative pathway critical for the removal of toxic, aggregate-prone proteins accumulating in neuro degenerative diseases. We found that the microglial-derived CCL-3/-4/-5 bind and activate neuronal CCR5,
which in turn promotes mTORC1 activation and disrupts autophagy and aggregate-prone protein clearance.
CCR5 and its cognate chemokines are upregulated in the brains of pre-manifesting mouse models for Huntington’s disease (HD) and tauopathy, suggesting a pathological role of this microglia-neuronal axis in the
early phases of these diseases. CCR5 upregulation is self-sustaining, as CCL5-CCR5 autophagy inhibition impairs CCR5 degradation itself. Finally, pharmacological or genetic inhibition of CCR5 rescues mTORC1 hyperactivation and autophagy dysfunction, which ameliorates HD and tau pathologies in mouse models.
in Article:
Importantly, genetic depletion or pharmacological inhibition of CCR5 by MVC reversed the defective autophagy-mediated degradation of neurotoxic proteins and the dysfunctional behavior associated with HD and tau pathology mouse models—a result that could have substantial clinical implications.
Our studies mainly focused on the harmful effects of elevated CCR5 signaling in neurons. However, as CCR5 is also expressed in other cell types (like macrophages, microglia, astrocytes), we cannot exclude that the beneficial effects associated with its inhibition might additionally be due to the suppression of its signaling outside the neuronal network.
We have known for some time that Leronlimab can go through the BB much readily that Maraviroc, so, whatever results were obtained with this can be potentiated with Leronlimab.
This indication only should be worth few "fingers" of SP. If you know what I mean ...
In the mean-time let's continue accumulating at these bargain prices