Someone asked me about Parkinson's disease. Wh

Someone asked me about Parkinson's disease.

When I put together the disease list I dove deep into each indication before it made it to the list. On the neurodegenerative/neuromuscular degenerative diseases I went even deeper because it isn't as straightforward as other diseases. I probably went through well over a thousand papers for those indication.

Here are some links to medical papers -

Low-Dose Maraviroc, an Antiretroviral Drug, Attenuates the Infiltration of T Cells into the Central Nervous System and Protects the Nigrostriatum in Hemiparkinsonian Monkeys

Why I do very deep dives is that sometimes you have to make your own logical conclusions from reports from numerous papers.

One of the hallmarks in Parkinson's disease is a drop in dopaminergic neurons and the rise of acetylcholine and the appearance of Lewy's bodies in commonality with Lewy's body dementia. A drop in dopaminergic neurons, the rise of acetylcholine and Lewy's bodies are associated with loss of motor control. Dendritic spine impairment will cause disregulated T-cell response that leads to the overactivated T-cells damaging neuronal sheaths and killing neurons including dopaminergic neurons.

Quote:

---

In PD, DCs contribute to disease progression through the presentation of α-synuclein to T cells, leading to an adaptive immune response against neuronal elements.
Dendritic cells in Parkinson's disease: Regulatory role and therapeutic potential

---

Quote:

---

We report that either αSyn overexpression or αSyn pre-formed fibrils (PFFs) treatment triggers the formation of cofilin-actin rods, synapse disruptors, in cultured hippocampal neurons and in the hippocampus of synucleinopathy mouse models and of LBD patients. In vivo, cofilin pathology is present concomitantly with synaptic impairment and cognitive dysfunction. Rods generation prompted by αSyn involves the co-action of the cellular prion protein (PrPC) and the chemokine receptor 5 (CCR5). Importantly, we show that CCR5 inhibition, with a clinically relevant peptide antagonist, reverts dendritic spine impairment promoted by αSyn. Collectively, we detail the cellular and molecular mechanism through which αSyn disrupts hippocampal synaptic structure and we identify CCR5 as a novel therapeutic target to prevent synaptic impairment and cognitive dysfunction in LBD. α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPC-CCR5 dependent pathway

---

Quote:

---

In Parkinson's disease (PD), neurotoxic microglia, Th1 cells, and Th17 cells are overactivated. Overactivation of these immune cells exacerbates the disease process and leads to the pathological development of pro-inflammatory cytokines, chemokines, and contact-killing compounds, causing the loss of dopaminergic neurons

This may be due to the pro-inflammatory cytokines (IL-1β, TNF-α, chemokines) released by overactivated neurotoxic microglia that alter the brain homeostasis, making it more favorable for microglia conversion to neurotoxic, thus causing neurotoxic microglia proliferation and release of inflammatory cytokines. In addition, TNF-α released from neurotoxic microglia can directly induce apoptosis by binding to the tumor necrosis factor receptor-1 (TNFR1) of dopaminergic neurons

In contrast, neurotoxic microglia in PD cause further neuronal damage by releasing pro-inflammatory cytokines that convert astrocyte phenotype to the neurotoxic A1 type,
The reciprocal interactions between microglia and T cells in Parkinson’s disease: a double-edged sword

---

RANTES-induced invasion of Th17 cells into substantia nigra potentiates dopaminergic cell loss in MPTP mouse model of Parkinson's disease

Shows maraviroc lowers acetylcholine when there are high levels of CCL5.

Concentration-effect curves to acetylcholine in aortae from CCR5+/+ mice incubated with vehicle or CCL5 (100ng/ml, 24h) in the presence of Maraviroc (40μM) (E).