Lrrk2 and alpha-synuclein are co-regulated in rodent striatum.
LRRK2, alpha-synuclein, UCH-L1 and DJ-1 are implicated in the etiology of Parkinson's disease. We show for the first time that increase in striatal alpha-synuclein levels induce increased Lrrk2 mRNA levels while Dj-1 and Uch-L1 are unchanged. We also demonstrate that a mouse strain lacking the dopamine signaling molecule DARPP-32 has significantly reduced levels of both Lrrk2 and alpha-synuclein, while mice carrying a disabling mutation of the DARPP-32 phosphorylation site T34A or lack alpha-synuclein do not show any changes. To test if striatal dopamine depletion influences Lrrk2 or alpha-synuclein expression, we used the neurotoxin 6-hydroxydopamine in rats and MitoPark mice in which there is progressive degeneration of dopamine neurons. Because striatal Lrrk2 and alpha-synuclein levels were not changed by dopamine depletion, we conclude that Lrrk2 and alpha-synuclein mRNA levels are possibly co-regulated, but they are not influenced by striatal dopamine levels.
Westerlund
Marie
M
Department of Neuroscience, Karolinska Institutet, Retzius väg 8 B2:4, S-17177 Stockholm, Sweden.
Ran
Caroline
C
Borgkvist
Anders
A
Sterky
Fredrik H
FH
Lindqvist
Eva
E
Lundströmer
Karin
K
Pernold
Karin
K
Brené
Stefan
S
Kallunki
Pekka
P
Fisone
Gilberto
G
Olson
Lars
L
Galter
Dagmar
D
D000818:Animals; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016627:Oxidopamine / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497929:Ppp1r1b protein, mouse; D051844:alpha-Synuclein; D016627:Oxidopamine; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004298:Dopamine