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Table 1 Summary of changes of V-ATPase and neurodegenerative diseases

From: The emerging roles of vacuolar-type ATPase-dependent Lysosomal acidification in neurodegenerative diseases

GeneDiseasesSpecies/modelPathological MechanismsReference
V0a1Alzheimer Disease5 × FAD micedecrease of N-glycosylation of V0a1[176]
PS/APP micedecrease of mature V0a1 in the lysosomal fraction[181]
V0a2Autosomal recessive cutis laxa typeII/Wrinkly Skin Syndromehumanabnormal glycosylation of serum proteins (CDG-II) and impairment of Golgi trafficking by V0a2 mutation[182,183,184,185]
V0a3Autosomal recessive osteopetrosis with neurodegenerationR444L mutant miceendoplasmic reticulum retention and misprocessing of V0a3 due to R444L mutation[186]
humanloss of V0a3 function due to truncation or impaired splicing caused by mutations[187, 188]
V0a4Renal Tubular Acidosis with hearing losshumanmutations[189]
V0a4−/− miceproximal tubule dysfunction with defective endocytic trafficking and accumulation of lysosomal material with V0a4 knockout[190, 191]
V1B1Renal Tubular Acidosis with hearing losshumanmutations[189]
V1B2Zimmermann-Laband syndromehumanimpaired complex assembly due to missense mutation[192]
Dominant Deafness-Onychodystrophy syndromehumanc.1516C > T mutation[193]
cognitive deficitsATPV1B2 mutant miceweaker interaction with the V1E2E and abnormal brain development[194]
ATP6AP2X-linked mental retardation and epilepsyhumanimpairment of ERK1/2 activation[127]
X-linked Parkinson Diseasehumanoverexpression of a minor splice isoform due to mutation[128]
cognitive impairmentATP6AP2 conditional knockout Drosophila/micedefects in presynaptic transmission and synapses abnormal caused by conditional knockout[179]
ATP13A2Neuronal ceroid lipofuscinosishumanmutation[195]
ATP13A2 ko miceincreased insoluble α-synuclein in the hippocampus[196]
Kufor-Rakeb syndromeATP13A2 ko miceincrease in gliosis, lipofuscinosis and lysosomal markers; protein aggregation but no α-synuclein abnormalities; selective defects in autophagy[197]
Hereditary parkinsonismhuman/in vitroretaintion in the endoplasmic reticulum and degradation by the proteasome due to truncation[198]
WFS1Wolfram Syndromehumanmutation[130]
WFS1−/− miceV1A/V1B instability[199]
CLN1Neuronal ceroid lipofuscinoseshumanmutation[139]
CLN1−/− micemisrouting of V-ATPase subunit V0a[141]