Current consensus is targeted RIPK1 would be enough.
Of the targets you mention I know most about TDP43 - that's the major dysfunctional protein in ALS and also frontotemporal dementia. A misfolded form of TDP43 called pathologic TDP43 is the major observable brain pathology in ALS. But nobody really knows if the issue is loss of function of the protein (it is used in RNA processing) or whether it is a symptomatic response to something else.
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