Angiotensin II protects against alpha-synuclein toxicity and reduces protein aggregation in vitro.
In this study, we examined the effects of angiotensin II (AngII) in a genetic in vitro PD model produced by alpha-synuclein (alpha-syn) overexpression in the human neuroglioma H4 cell line. We observed a maximal decrease in alpha-syn-induced toxicity of 85% and reduction in inclusion formation by 19% when cultures were treated with AngII in the presence of the angiotensin type 1 (AT1) receptor antagonist losartan and AT2 receptor antagonist PD123319. When compared to AngII, the AT4 receptor agonist AngIV was moderately effective in protecting H4 cells against alpha-syn toxicity and did not significantly reduce inclusion formation. Here we show that AngII is protective against genetic, as well as neurotoxic models of PD. These data support the view that agents acting on the renin-angiotensin-system (RAS) may be useful in the prevention and/or treatment of Parkinson's disease.
Grammatopoulos
Tom N
TN
MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA. thangram@hotmail.com
Outeiro
Tiago F
TF
Hyman
Bradley T
BT
Standaert
David G
DG
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D002479:Inclusion Bodies / Q000187:drug effects / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C090830:AT4 receptor; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D051844:alpha-Synuclein; D000804:Angiotensin II; C073402:PD 123319; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D019808:Losartan