Editing Vesicular monoamine transporter (section)

==Clinical significance==
VMAT2 has been shown to contribute to many clinical neurological disorders including drug addiction, mood disorders, and stress,<ref>{{cite journal |vauthors=Tillinger A, Sollas A, Serova LI, Kvetnansky R, Sabban EL | year = 2010 | title = Vesicular monoamine transporters (VMATs) in adrenal chromaffin cells: stress-triggered induction of VMAT2 and expression in epinephrine synthesizing cells | journal = Cell Mol Neurobiol | volume = 30 | issue = 8| pages = 1459–1465 | doi =  10.1007/s10571-010-9575-z| pmid = 21046458 | s2cid = 21852075 | pmc = 11498772 }}</ref> as well as Parkinson's disease<ref>{{cite journal |vauthors=Okamura N, Villemagne VL, Drago J, Pejoska S, Dhamija RK, Mulligan RS, Ellis JR, Ackermann U, O'Keefe G, Jones G, Kung HF, Pontecorvo MJ, Skovronsky D, Rowe CC | year = 2010 | title = In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson disease with (18)F-AV-133 | journal = J. Nucl. Med. | volume = 51 | issue = 2| pages = 223–228 | doi=10.2967/jnumed.109.070094 | pmid=20080893| doi-access = free }}</ref> and Alzheimer's disease.<ref>{{cite journal |vauthors=Villemagne VL, Okamura N, Pejoska S, Drago J, Mulligan RS, Chetelat G, Ackermann U, O'Keefe G, Jones G, Gong S, Tochon-Danguy H, Kung HF, Masters CL, Skovronsky DM, Rowe CC | year = 2011 | title = In vivo assessment of vesicular monoamine transporter type 2 in dementia with lewy bodies and Alzheimer disease | journal = Arch. Neurol. | volume = 68 | issue = 7| pages = 905–912 | doi=10.1001/archneurol.2011.142| pmid = 21747030 | doi-access = free }}</ref><ref>{{cite journal |vauthors=Salin A, Savli M, Lanzenberger R | year = 2011 | title = Serotonin and molecular neuroimaging in humans using PET | journal = Amino Acids | volume = 42 | issue = 6| pages = 2039–57 | doi = 10.1007/s00726-011-1078-9 | pmid = 21947614 | s2cid = 14118396 }}</ref>

===Parkinson's disease===
Studies indicate VMAT2 mRNA is present in all cell groups damaged by Parkinson's disease (PD);<ref name="Miller GW 1999 PII">{{cite journal |vauthors=Miller GW, Gainetdinov RR, Levey AI, Caron MG | year = 1999 | title = Dopamine transporters and neuronal injury | journal = TiPS | volume = 20 | issue = 10 | page = 425 | doi = 10.1016/s0165-6147(99)01379-6 | pmid = 10498956 }}</ref> these findings have identified VMAT2 as a target for preventing Parkinson's. VMAT2 presence does not independently protect neurons from PD, but a decrease in VMAT2 expression has been shown to correlate with susceptibility to the disease,<ref name="Miller GW 1999 PII"/> which may be due to a ratio between the [[dopamine transporter]] and VMAT2.<ref name="Miller GW 1999 PII"/>

Based on the understanding the increased cytosolic dopamine levels lead to dopaminergic cell death in PD, it has been proposed that regulatory [[Polymorphism (biology)|polymorphisms]] in VMAT2 affect VMAT2 quantitative expression, and may serve as a genetic risk factor for PD. Specifically, the SLC18A2 [[Promoter (genetics)|promoter region]] for the VMAT2 gene has been identified as an area where several polymorphisms form discrete [[haplotype]]s.<ref name="Wimalasena, K. 2011"/><ref name="Glatt CE, Wahner AD, White DJ, Ruiz-Linares A, Ritz B 2006 299–305">{{cite journal |vauthors=Glatt CE, Wahner AD, White DJ, Ruiz-Linares A, Ritz B | year = 2006 | title = Gain-of-function haplotypes in the vesicular monoamine transporter promoter are protective for Parkinson disease in women | journal = Hum. Mol. Genet. | volume = 15 | issue = 2| pages = 299–305 | doi=10.1093/hmg/ddi445| pmid = 16339215 | pmc = 3643966 }}</ref>

===Mood disorders===
Studies using a genetic rodent model to understand clinical depression in humans suggest that VMAT2 genetic or functional alterations may be involved in depression.<ref>{{cite journal |vauthors=Schwartz K, Yadid G, Weizman A, Rehavi M | year = 2003 | title = Decreased limbic vesicular monoamine transporter 2 in a genetic rat model of depression | journal = Brain Res. | volume = 965 | issue = 1–2| pages = 174–179 | doi=10.1016/s0006-8993(02)04167-7| pmid = 12591135 | s2cid = 26761996 }}</ref> Reduced VMAT2 levels were identified in specific subregions of the [[striatum]] involved in clinical depression, including the [[nucleus accumbens]] shell but not the core, the [[ventral tegmental area]], and the [[substantia nigra]]'s [[pars compacta]]. The reduced VMAT2 protein levels were not accompanied by similar levels of VMAT2 mRNA alterations. Based on these findings, it has been proposed that VMAT2 activity is not altered at the level of genetic expression, but may be altered at the functional level in ways that may correlate with clinical depression.<ref name="Wimalasena, K. 2011"/>

===Drug addiction===
Many [[psychostimulant]] drugs are known to interact with VMAT, including amphetamine analogs such as methamphetamine, cocaine, and ecstasy (MDMA).{{cn|date=November 2023}}