A molecular link between the active component of marijuana and Alzheimer's disease pathology
A molecular link between the active component of marijuana and Alzheimer's disease pathology
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DOI：
10.1021/mp060066m
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发表时间：
2006-11-01
影响因子：
4.9
通讯作者：
Janda, Kim D.
中科院分区：
文献类型：
--
作者：
Eubanks, Lisa M.;Rogers, Claude J.;Janda, Kim D.
阿尔茨海默病是导致老年人痴呆症的主要原因，随着这一人口规模的不断扩大，阿尔茨海默氏症的病例预计在未来50年内增加两倍。因此，开发延缓或阻止疾病发展的治疗方法已成为提高患者生活质量和降低可归因于阿尔茨海默病的医疗成本的当务之急。在这里，我们证明了大麻的活性成分Delta(9)-四氢大麻酚(THC)竞争性地抑制乙酰胆碱酯酶(AChE)，并阻止AChE包含的淀粉样β蛋白(Aβ)聚集，这是阿尔茨海默病的关键病理标志。对THC-AChE相互作用的计算机模拟显示，THC结合在AChE的外周阴离子位置，这是参与淀粉样蛋白形成的关键区域。与目前批准的治疗阿尔茨海默病的药物相比，THC是一种相当优越的Aβ聚集抑制剂，这项研究提供了一种以前未知的分子机制，通过这种机制，大麻类分子可能直接影响这种衰弱疾病的进展。
Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients and reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Delta(9)-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-incluced amyloid beta-peptide (A beta) aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of A beta aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.