Iacono R P, Sandyk R
Int J Neurosci. 1987 Feb;32(3-4):710-4.
Although the "cholinergic hypothesis" of the pathophysiology of Alzheimer's disease has received great attention during the past years, it has recently come under increasing criticism specifically owing to failure of therapeutic endeavors based on this premise. As the potential broad role of the intrinsic opioids in the neurochemical modulation of diverse brain functions emerges, the realization that these data may be reconciled to a unifying hypothesis underlying the nature of some chronic dementing diseases (including Alzheimer's disease, Korsakoff disease and Parkinson's disease) occurs. Certain specific characteristics of the known pathologic changes and neurotransmitter deficits of Alzheimer's disease may be explained based on an early vulnerability of the hypothalamus combined with derangements of endorphinergic functions which follow. The latter may be implicated in the subsequent degeneration of structures receiving projections from the arcuate nucleus of the hypothalamus. This is based on the known role of endorphins in the modulation of central neurotransmitters and specifically acetylcholine activity. In addition, the reciprocal neuroendocrine and neuroimmunologic interactions mediated through the hypothalamus, may be of further importance in the evolution of Alzheimer's disease.
尽管阿尔茨海默病病理生理学的“胆碱能假说”在过去几年受到了极大关注，但最近因其基于该假说的治疗尝试失败而受到越来越多的批评。随着内源性阿片类物质在多种脑功能神经化学调节中的潜在广泛作用逐渐显现，人们开始意识到这些数据可能与一些慢性痴呆疾病（包括阿尔茨海默病、科萨科夫综合征和帕金森病）本质的统一假说相契合。阿尔茨海默病已知病理变化和神经递质缺陷的某些特定特征，可基于下丘脑的早期易损性以及随后内啡肽能功能紊乱来解释。后者可能与接受下丘脑弓状核投射的结构随后的退化有关。这是基于内啡肽在调节中枢神经递质尤其是乙酰胆碱活性方面的已知作用。此外，通过下丘脑介导的相互神经内分泌和神经免疫相互作用，在阿尔茨海默病的发展过程中可能具有更重要的意义。
