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Here is an abstract explaining how mislocation and aggregation, of TPD-43, is caused by inflammation.

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Nice article. I posted my previous comment on mitochondrial dysfunction in NASH because excessive TPD-43 is also implicated in mitochondrial dysfunction. TPD-43 can also be overexpressed in the hypothalamus negatively affecting the Hypothalamic Pituitary Axis.

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Ultimately TDP-43 may act as a default suppressor of the NF-κβ transactivation pathway. Conversely, the blockage of NF-κβ nuclear translocation by overexpression of TDP-43 is preventable by simultaneous overexpression of p65. In a previous study by Swarup and colleagues, while it was demonstrated that TDP-43 interacts and serves as a coactivator of NF-κβ in cultured cells including neurons and glia, contrastingly it was demonstrated that TDP-43 itself does not activate NF-kβ or upregulate p65. Rather a second hit or inflammatory trigger (e.g., LPS, PAMPs, or cytokines) is required to cause NF-kβ activation via TLR signalling. In conjunction with this second hit, TDP-43 overexpression can enhance NF-kβ activation and the deregulation of TDP-43 may contribute to ALS pathogenesis in part by this enhancement.

In addition to the role TDP-43’s NLS may play in the interaction with NF-κβ/p65, other key structures of TDP-43 such as the RRM1 domain may also play a facilitatory role. The sensitivity of the RRM1 domain in TDP-43 proteinopathy has been highlighted and oxidation of the RRM1 domain results in cytosolic mislocalisation with irreversible protein aggregation. Interestingly, aside from RNA metabolism, the RRM1 domain itself is responsible for the interaction between TDP-43 and p65. This interaction mediates overactivation of the NF-κβ pathway and results in a heightened vulnerability of neurons to injury and a hyperactive inflammatory response of glial cells. The abnormal binding of p65 to the RRM1 domain of TDP-43 is also proposed to interfere with normal protein folding or RNA binding, resulting in TDP-43 aggregation in the cytoplasm.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346169/

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A secondary inflammatory hit is necessary to cause NF-kb/TDP-43 to go out of control. CCR5 certainly presents many inflammatory hits. NF-kb is downregulated by leronlimab breaking that cycle.