2026-10-13T03:03:07Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33983521 2026-09-24T12:22:47Z category_15 portal_316 item_type_3 month_year_09_2026

Table 1_Minding the gates: dual cell-autonomous and non-cell-autonomous mechanisms of TBK1 in ALS/FTD.pdf Julie Smeyers (20943075) Daniel A. Mordes (8399244) Neuroscience ALS FTD cell autonomous non-cell-autonomous in vivo models TBK1 <p>Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) comprise a neurodegenerative disease spectrum characterized by TDP-43 pathology and overlapping genetic risk factors. Loss-of-function variants in TBK1 (TANK-binding kinase 1) represent one of the most common genetic causes of ALS/FTD, highlighting haploinsufficiency for TBK1 as a major contributor to disease pathogenesis. Emerging evidence from iPSC and mouse models suggests that reduced TBK1 activity disrupts interconnected autophagy, endo-lysosomal, and innate immune pathways through both cell-autonomous and non-cell-autonomous mechanisms. In this review, we discuss the multifaceted role of TBK1 as a master regulator of proteostasis and inflammatory pathways, highlight its critical role in maintaining microglial homeostasis, and explore how these convergent functions inform therapeutic strategies for ALS/FTD.</p> 2026-09-24T12:22:47Z Dataset Dataset 10.3389/fnins.2026.1941293.s001 https://figshare.com/articles/dataset/Table_1_Minding_the_gates_dual_cell-autonomous_and_non-cell-autonomous_mechanisms_of_TBK1_in_ALS_FTD_pdf/33983521 CC BY 4.0