Sharma A, Parikh V, Singh M
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
Indian J Exp Biol. 1997 Nov;35(11):1146-55.
Alzheimer's disease is a progressive neurodegenerative disorder primarily manifesting as a loss of memory. Senile plaques and neurofibrillary tangles are the major histopathological alteration in the brain of Alzheimer's disease patients. A considerable deficiency of cholinergic neurons is a consistent finding in Alzheimer's disease. Therefore, many therapeutic strategies to augment cerebral concentration of acetylcholine such as cholinergic precursors, cholinergic receptor agonists, cholinesterase inhibitors and acetylcholine release modulators have been evaluated in Alzheimer's disease. Although cholinesterase inhibitors such as tacrine and galanthamine offer modest clinical benefits, other cholinergic agents have proved to be of limited therapeutic value. Efforts to enhance monoaminergic neurotransmission have also been largely disappointing. Therefore, emphasis is not being put on the use of combination of two class of drugs. Moreover, use of therapeutic agents based on the putative pathogenic etiology of the disease such as excitotoxicity, amyloidosis, aluminium accumulation, inflammatory mechanisms and free radical production is being evaluated. Desferrioxamine, non-steroidal anti-inflammatory drugs, prednisone, dapsone, vitamin E and idebenone are some such agents that are currently under investigation for the preventive or palliative effect in Alzheimer's disease. Neurotrophic factors such as nerve growth factor, brain derived neurotrophic factor and epidermal growth factor have shown promising results in animal studies. However, novel methods for delivering these molecules into the brain required to be developed before launching their clinical trials in man.
阿尔茨海默病是一种进行性神经退行性疾病，主要表现为记忆力丧失。老年斑和神经原纤维缠结是阿尔茨海默病患者大脑中的主要组织病理学改变。胆碱能神经元的显著缺乏是阿尔茨海默病中一致的发现。因此，许多增加大脑中乙酰胆碱浓度的治疗策略，如胆碱能前体、胆碱能受体激动剂、胆碱酯酶抑制剂和乙酰胆碱释放调节剂，已在阿尔茨海默病中进行了评估。尽管他克林和加兰他敏等胆碱酯酶抑制剂有一定的临床益处，但其他胆碱能药物已被证明治疗价值有限。增强单胺能神经传递的努力也大多令人失望。因此，人们没有将重点放在两类药物的联合使用上。此外，正在评估基于疾病假定致病病因（如兴奋性毒性、淀粉样变性、铝蓄积、炎症机制和自由基产生）的治疗药物的使用。去铁胺、非甾体抗炎药、泼尼松、氨苯砜、维生素E和艾地苯醌是目前正在研究其对阿尔茨海默病预防或姑息作用的一些此类药物。神经生长因子、脑源性神经营养因子和表皮生长因子等神经营养因子在动物研究中已显示出有希望的结果。然而，在开展人体临床试验之前，需要开发将这些分子输送到大脑的新方法。
