Neurite outgrowth in PC12 cells stimulated by acetyl-L-carnitine arginine amide.

Abstract:

:Senescence of the central nervous system is characterized by a progressive loss of neurons that can result in physiological and behavioral impairments. Reduction in the levels of central neurotrophic factors or of neurotrophin receptors may be one of the causes of the onset of these degenerative events. Thus, a proper therapeutic approach would be to increase support to degenerating neurons with trophic factors or to stimulate endogenous neurotrophic activity. Here we report that acetyl-L-carnitine arginine amide (ST-857) is able to stimulate neurite outgrowth in rat pheochromocytoma PC12 cells in a manner similar to that elicited by nerve growth factor (NGF). Neurite induction by ST-857 requires de novo mRNA synthesis and is independent of the action of several common trophic factors. The integrity of the molecular structure of ST-857 is essential for its activity, as the single moieties of the molecule have no effect on PC12 cells, whether they are tested separately or together. Also, minor chemical modifications of ST-857, such as the presence of the arginine moiety at a position other than the amino one, completely abolish its neuritogenic effect. Lastly, the presence of ST-857 in the culture medium competes with the high affinity NGF binding in a dose dependent fashion. These results, although preliminary, are suggestive of a possible role for ST-857 in the development of therapeutic strategies to counteract degenerative diseases of the CNS.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Taglialatela G,Navarra D,Olivi A,Ramacci MT,Werrbach-Perez K,Perez-Polo JR,Angelucci L

doi

10.1007/BF00995145

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

1-9

issue

1

eissn

0364-3190

issn

1573-6903

journal_volume

20

pub_type

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