Stimulation of neurotrophin synthesis by 4-methylcatechol: a promising approach for neuroprotection

Neurotrophins play a crucial role in the differentiation, maintenance, and survival of various types of peripheral and central neurons. However, the therapeutic use of neurotrophins is limited by their inability to cross the blood-brain barrier and their instability in the bloodstream. One of the promising approaches to utilize neurotrophic actions of these molecules in the therapy of neurodegenerative diseases is the stimulation of neurotrophin synthesis. Here we review the effects of 4-methylcatechol, a nonadrenergic catechol compound, on the synthesis of the neurotrophins nerve growth factor and brain-derived neurotrophic factor in the peripheral and central nervous system. The neuroprotective potential of 4-methylcatechol in animal models of neurodegenerative disorders is discussed, and other agents that enhance neurotrophin synthesis are also mentioned.Biomedical Reviews 1999; 10: 45-54

<Abstract of published report>Stimulation of Nerve Growth Factor Synthesis/Secretion by 1,4-Benzoquinone and Its Derivatives in Cultured Mouse Astroglial Cells

AbstractPreviously we reported that astroglial cells cultured from mouse brain synthesize and secrete nerve growth factor (NGF) and that, in quiescent cells, catecholamines markedly increase the NGF content in the conditioned medium (CM). We wished to further assess the structural properties required for exhibition of such effect of compounds containing a ring structure analogous to that of catechol on astroglial NGF synthesis. During our study, we found that hydroquinone, which was confirmed not to stimulate NGF synthesis in mouse flbroblast cells in another of our investigations, is a potent stimulator of NGF synthesis in astroglial cells and that 1,4-benzoquinone, an oxidized form of hydroquinone, is a more effective stimulator than hydroquinone itself. In addition, the results of experiments with 1,2-benzoquinone derivatives indicated that the presence of a long aliphatic side chain in the molecule eliminates the stimulatory effect of 1,4-benzoquinone on NGF synthesis in astroglial cells