Article

Enhanced legumain activity links progranulin deficiency to TDP-43 pathology in frontotemporal lobar degeneration

2024-01-16

Abstract excerpt

Loss-of-function mutations in GRN are a major cause of frontotemporal lobar degeneration (FTLD) with TDP-43-positive inclusions. Progranulin (PGRN) loss leads to lysosomal dysfunction, microglial hyperactivation, and TDP-43 deposition, yet the underlying pathomechanism remains unknown. We demonstrate that PGRN slows the maturation and limits the proteolytic activity of the lysosomal protease legumain (LGMN). Acco...

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Literature Corpus work: ed82bc21-3139-5049-a044-9f681b183e47
DOI: 10.1101/2024.01.16.575687

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