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

Song, Qiaoyun; Meng, Bo; Xu, Haidong; Mao, Zixu

doi:10.1186/s40035-020-00196-0

Translational Neurodegeneration

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

Gene	Diseases	Species/model	Pathological Mechanisms	Reference
V0a1	Alzheimer Disease	5 × FAD mice	decrease of N-glycosylation of V0a1	[176]
V0a1	Alzheimer Disease	PS/APP mice	decrease of mature V0a1 in the lysosomal fraction	[181]
V0a2	Autosomal recessive cutis laxa typeII/Wrinkly Skin Syndrome	human	abnormal glycosylation of serum proteins (CDG-II) and impairment of Golgi trafficking by V0a2 mutation	[182,183,184,185]
V0a3	Autosomal recessive osteopetrosis with neurodegeneration	R444L mutant mice	endoplasmic reticulum retention and misprocessing of V0a3 due to R444L mutation	[186]
V0a3	Autosomal recessive osteopetrosis with neurodegeneration	human	loss of V0a3 function due to truncation or impaired splicing caused by mutations	[187, 188]
V0a4	Renal Tubular Acidosis with hearing loss	human	mutations	[189]
V0a4	Renal Tubular Acidosis with hearing loss	V0a4−/− mice	proximal tubule dysfunction with defective endocytic trafficking and accumulation of lysosomal material with V0a4 knockout	[190, 191]
V1B1	Renal Tubular Acidosis with hearing loss	human	mutations	[189]
V1B2	Zimmermann-Laband syndrome	human	impaired complex assembly due to missense mutation	[192]
	Dominant Deafness-Onychodystrophy syndrome	human	c.1516C > T mutation	[193]
	cognitive deficits	ATPV1B2 mutant mice	weaker interaction with the V1E2E and abnormal brain development	[194]
ATP6AP2	X-linked mental retardation and epilepsy	human	impairment of ERK1/2 activation	[127]
	X-linked Parkinson Disease	human	overexpression of a minor splice isoform due to mutation	[128]
	cognitive impairment	ATP6AP2 conditional knockout Drosophila/mice	defects in presynaptic transmission and synapses abnormal caused by conditional knockout	[179]
ATP13A2	Neuronal ceroid lipofuscinosis	human	mutation	[195]
	Neuronal ceroid lipofuscinosis	ATP13A2 ko mice	increased insoluble α-synuclein in the hippocampus	[196]
	Kufor-Rakeb syndrome	ATP13A2 ko mice	increase in gliosis, lipofuscinosis and lysosomal markers; protein aggregation but no α-synuclein abnormalities; selective defects in autophagy	[197]
	Hereditary parkinsonism	human/in vitro	retaintion in the endoplasmic reticulum and degradation by the proteasome due to truncation	[198]
WFS1	Wolfram Syndrome	human	mutation	[130]
WFS1	Wolfram Syndrome	WFS1−/− mice	V1A/V1B instability	[199]
CLN1	Neuronal ceroid lipofuscinoses	human	mutation	[139]
CLN1	Neuronal ceroid lipofuscinoses	CLN1−/− mice	misrouting of V-ATPase subunit V0a	[141]

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ISSN: 2047-9158

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