Bart Tummers

Abstract Neurodegenerative diseases are frequently associated with proteotoxic stress linked to disease specific proteins. The autophagy-lysosome system provides essential control of proteotoxic stress and its failure can lead to initiation of apoptosis. However, in aging and neurodegenerative diseases apoptosis is insufficient to account for all neuronal death, and several different cell death types have been reported in these contexts.

Necroptosis relies on interactions between RIP Homotypic Interaction Motif (RHIM)-containing proteins to form an RHIM-amyloid structure called the necrosome. Recent findings by Wu et al. in Cell Research now demonstrate that HSPA8, a member of the 70-kDa heat shock protein (HSP70) family, negatively regulates necroptosis by inhibiting and reversing RHIM-amyloid fibril formation, thereby safeguarding tissues from damage.

(Cell 178, 536–551.e1–e14; July 25, 2019) Our paper focused on the identification of LC3-associated endocytosis and the role of this pathway in the clearance of beta-amyloid and mitigation of neurodegeneration in Alzheimer’s Disease. Following publication, we have identified two errors in the original version of the article. First, the same FACS plot for TMEM119 expression was inadvertently presented for both 5xFAD/Rubicon +/− and 5xFAD/Rubicon −/− as shown in Figure S5C.