Dual roles for autophagy: degradation and secretion of Alzheimer's disease Aβ peptide.
Alzheimer's disease (AD) is a neurodegenerative disease exhibiting amyloid beta (Aβ) peptide accumulation as a key characteristic. Autophagy, which is dysregulated in AD, participates in the metabolism of Aβ. Unexpectedly, we recently found that autophagy, in addition to its degradative function, also mediates the secretion of Aβ. This finding adds Aβ to an increasing number of biomolecules, the secretion of which is mediated by autophagy. We also showed that inhibition of Aβ secretion through genetic deletion of autophagy leads to intracellular Aβ accumulation, which enhanced neurodegeneration induced by autophagy deficiency. Hence, autophagy may play a central role in two pathological hallmarks of AD: Aβ amyloidosis and neurodegeneration. Herein, we summarize the role of autophagy in AD with focus on Aβ metabolism in light of the recently established role of autophagy in protein secretion. We discuss potential routes for autophagy-mediated Aβ secretion and suggest experimental approaches to further elucidate its mechanisms.
Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama, Japan; KI-Alzheimer's Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, Huddinge, Sweden.
Per
P
Nilsson
Takaomi C
TC
Saido
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D006801:Humans; D008954:Models, Biological; D059748:Proteolysis
D016229:Amyloid beta-Peptides
Alzheimer's disease; Aβ secretion; autophagy; neurodegeneration