Stimulation of Neurotrophin Synthesis by 4-Methyl Catechol: An Approach to the Treatment of Neurodegeneration

Abstract

The family of neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3,and NT-4/5 plays a crucial role in the differentiation, maintenance, and survival of distinct and overlapping neuronal populations within the central and peripheral nervous systems, respectively. In addition, neurotrophins are related to neuronal plasticity. Neurotrophins are widely distributed in the CNS, and are expressed at the highest level in the hippocampus and cerebral cortex. Expression of both mRNA^NGF and mRNA^BDNF is known to be regulated by neurotransmission (1), and evoked in association with neural injuries. These observations suggest an involvement of neurotrophins in the process of neuronal degeneration and regeneration. Indeed, intraventricular administration of BDNF prevents neuronal death of the nigral dopaminergic neurons induced by infusion of neurotoxins or axotomy of the nigrostriatal pathway (2). Likewise, administration of NGF or BDNF suppresses neuronal death in the hippocampal pyramidal neurons following transient forebrain ischemia (3). Therefore, BDNF in particular, which has much wider action spectrum than NGF, is expected as a therapeutic agent for neurological disorders, such as Parkinson’s disease, amyotrophic lateral screlosis, and Alzheimer’s disease. However, there are at least two obstacles against therapeutic application of neurotrophins to brain diseases. First, neurotrophins are macromolecules that cannot pass through the blood-brain barrier (BBB).