(300 WORDS MAX) Animal model and clinical trial studies demonstrate that neurotrophines including Nerve Growth Factor (NGF) and Brain-derived neurotrophic factor (BDNF) are useful for the treatment of Central Nerve System (CNS) diseases. These researches have shown NGF and BDNF have a beneficial effect in aged rats with memory deficits. Chronic administration of neurotrophins improves cholinergic function and survival as well as cognitive behavior in aged rats. Clinical administration of NGF or BDNF delays the onset of Alzheimer's disease (AD) and alleviates peripheral diabetic neuropathies. Unfortunately, due to their poor pharmacokinetics and bioavailability at the desired targets, NGF or BDNF does not make an ideal drug candidate. Recently, we have identified some unique compounds that are derivatives of naturally occurring gambogic acid that mimic NGF by acting as TrkA agonists and protect neurons from cell death. In vitro and animal studies demonstrate that gambogic amide possesses potent neurotrophic effects. Moreover, we have identified 7,8-dihydroxyflavone as a robust TrkB agonist. This compound displays significant neuroprotective effect in various animal models by mimicking BDNF. Hence, these small molecules provide a pharmacological intervention for clinical treatment of various neurological diseases including AD.