Neurotransmitter release: vacuolar ATPase V0 sector c-subunits in possible gene or cell therapies for Parkinson's, Alzheimer's, and psychiatric diseases.
We overview the 16-kDa proteolipid mediatophore, the transmembrane c-subunit of the V0 sector of the vacuolar proton ATPase (ATP6V0C) that was shown to mediate the secretion of acetylcholine. Acetylcholine, serotonin, and dopamine (DA) are released from cell soma and/or dendrites if ATP6V0C is expressed in cultured cells. Adeno-associated viral vector-mediated gene transfer of ATP6V0C into the caudate putamen enhanced the depolarization-induced overflow of endogenous DA in Parkinson-model mice. Motor impairment was ameliorated in hemiparkinsonian model mice when ATP6V0C was expressed with DA-synthesizing enzymes. The review discusses application in the future as a potential tool for gene therapy, cell transplantation therapy, and inducible pluripotent stem cell therapy in neurological diseases, from the view point of recent findings regarding vacuolar ATPase.
Kanazawa University Research Center for Child Mental Development, Kanazawa, 920-8640, Japan. haruhiro@med.kanazawa-u.ac.jp.
Haruhiro
H
Higashida
Kanazawa University Research Center for Child Mental Development, Kanazawa, 920-8640, Japan.
Shigeru
S
Yokoyama
Kanazawa University Research Center for Child Mental Development, Kanazawa, 920-8640, Japan.
Chiharu
C
Tsuji
Division of Neurology, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan.|Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
Shin-Ichi
SI
Muramatsu
D000544:Alzheimer Disease / Q000378:metabolism* / Q000628:therapy; D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D015316:Genetic Therapy; D006801:Humans; D001523:Mental Disorders / Q000378:metabolism* / Q000628:therapy; D010300:Parkinson Disease / Q000378:metabolism* / Q000628:therapy; D009435:Synaptic Transmission / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*
D025262:Vacuolar Proton-Translocating ATPases
ATPase; Gene therapy; IPSC; Neurotransmitter; Psychiatric diseases; Secretion