 |
 |
Synuclein-protein complexes render dopamine neurotoxic NEW YORK (Reuters Health) - Alpha-synuclein forms soluble complexes with the anti-apoptotic protein 14-3-3 that appear to cause endogenous dopamine to become toxic to neurons in the substantia nigra, according to a study in the June issue of Nature Medicine. This finding may explain the selective loss of dopaminergic neurons in Parkinson's disease, the study authors suggest, and it may ultimately lead to new therapies for the disease, as well as for diffuse Lewy-body disease and some variants of Alzheimer's disease. Dr. Bruce A. Yankner, of the Children's Hospital in Boston, told Reuters Health that "until now, the combination of alpha-synuclein with 14-3-3 protein was not known to cause neuron degeneration." Dr. Yankner and associates found that transfection of alpha-synuclein in primary cultures of nondopaminergic human cortical neurons (HCN cells) and in human fetal dopaminergic neurons (DAN cells) led to similar expression of the protein. Overexpression of alpha-synuclein increased survival of the HCN cells, but led to increased apoptosis in the DAN cells. They then inhibited endogenous dopamine expression in DAN cells and found that apoptosis induced by alpha-synuclein and potentiated by oxidative stress was completely blocked. Autopsy studies showed that alpha-synuclein in the substantia nigra was complexed with 14-3-3 protein. This inactivates the anti-apoptotic effect of 14-3-3 protein, and dopamine metabolism subsequently promotes apoptosis by acting as a source of reactive oxygen species, the authors suggest. They believe that the complexes may also increase neuronal vulnerability to other pro-oxidative agents, such as amyloid beta-protein. "It is too early to make any clear predictions regarding treatment," said Dr. Yankner. "However, if the findings of this paper prove to be important for Parkinson's disease, then preventing alpha-synuclein from getting together with the 14-3-3 protein could be a new therapeutic approach to the disease." Last Updated: 2002-05-31 14:17:45 -0400 (Reuters Health) By Karla Gale Nat Med 2002;8:600-606. Copyright 2002 Reuters Limited. http://www.reutershealth.com/archive/2002/05/31/professional/links/20020531s cie006.html janet paterson: an akinetic rigid subtype, albeit primarily perky, parky pd: 55/41/37 cd: 55/44/43 tel: 613 256 8340 email: [log in to unmask] smail: 375 Country Street, Almonte, Ontario, Canada, K0A 1A0 a new voice website: http://www.geocities.com/janet313/ ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn