Alternative therapy of Alzheimer's disease via supplementation with choline acetyltransferase.
Much evidence indicates that the memory and cognitive deficits of patients with Alzheimer's disease are closely associated with dysfunction of central cholinergic system. The degree of reduction of choline acetyltransferase activity in cerebral cholinergic neurons is significantly correlated with the severity of dementia or cognitive impairments observed in Alzheimer's disease. Therefore, Alzheimer's disease may be slowed by supplementation of exogenous choline acetyltransferase. Here we show that choline acetyltransferase mediated by TAT protein transduction domain passes through the blood-brain barrier and enters the neurons in mice, increasing choline acetyltransferase and neurotransmitter acetylcholine contents. The recombination TAT-choline acetyltransferase fusion protein injected intravenously improves the memory and cognitive dysfunction in Alzheimer's disease model mice induced by amyloid-beta peptide. Our results imply a novel and potentially effective way for Alzheimer's disease therapy.
Fu
Ai Ling
AL
Department of Biochemistry and Pharmacology, Institute of Pharmacology and Toxicology, Tai Ping Road, 27, 100850 Beijing, China.
Li
Qian
Q
Dong
Zhao Hui
ZH
Huang
Shi Jie
SJ
Wang
Yu Xia
YX
Sun
Man Ji
MJ
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000008:administration & dosage* / Q000096:biosynthesis; D000529:Complementary Therapies / Q000379:methods*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice
D002795:Choline O-Acetyltransferase