On the role of v-ATPase V0a1-dependent degradation in Alzheimer disease.

Williamson, W.R. and Hiesinger, P.R. – 2010

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.

Titel
On the role of v-ATPase V0a1-dependent degradation in Alzheimer disease.
Verfasser
Williamson, W.R. and Hiesinger, P.R.
Verlag
Taylor & Francis
Schlagwörter
Neurodegeneration, Autophagy, degradation, acidification, vesicular ATPase, Alzheimer
Datum
2010-11-01
Kennung
doi: 10.4161/cib.3.6.13364
Erschienen in
Commun Integr Biol 3(6): 604-7
Sprache
eng
Art
Text
Rechte
© 2010 Landes Bioscience
NeuroCure