title: On the role of v-ATPase V0a1-dependent degradation in Alzheimer disease.
abstract: Defective autophagy and lysosomal degradation are hallmarks of numerous neurodegenerative disorders. Vesicular ATPases are intracellular proton pumps that acidify autophagosomes and lysosomes. V0a1 is a key component of the v-ATPase that is only required in neurons in Drosophila melanogaster. We have recently shown that loss of V0a1 in Drosophila photoreceptor neurons leads to slow, adult-onset degeneration.1 Concurrently, Lee et al.2 reported that V0a1 fails to localize to lysosomal compartments in cells from Presenilin 1 knock-out cells. Together these two reports suggest that a neuronal V0a1-dependent degradation mechanism may be causally linked to Alzheimer pathology. Indeed, we now show that loss of V0a1 makes Drosophila neurons more susceptible to insult with human Alzheimer-related neurotoxic Aβ and tau proteins. Furthermore, we discuss the potential significance of the discovery of the neuron-specific degradation mechanism in Drosophila for intracellular degradation defects in Alzheimer Disease.
authors.affiliation: Department of Physiology and Green Center for Systems Biology; University of Texas Southwestern Medical Center at Dallas; Dallas, TX USA.
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Williamson
authors.forename: P Robin
authors.initials: PR
authors.lastname: Hiesinger