Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA; Department of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX 78712, USA; Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA.
Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA.
Biochem Pharmacol. 2014 Apr 15;88(4):584-93. doi: 10.1016/j.bcp.2013.11.010. Epub 2013 Dec 4.
This paper focuses on brain mitochondrial respiration as a therapeutic target for neuroprotection and cognitive enhancement. We propose that improving brain mitochondrial respiration is an important future direction in research and treatment of Alzheimer's disease (AD) and other conditions associated with cognitive impairment and neurodegeneration. The central thesis is that supporting and improving brain mitochondrial respiration constitutes a promising neurotherapeutic principle, with potential applications in AD as well as in a wide variety of neuropsychological conditions. We propose three different interventional approaches to improve brain mitochondrial respiration based on (a) pharmacology, (b) photobiomodulation and (c) nutrition interventions, and provide detailed examples for each type of intervention. First, low-dose USP methylene blue is described as a pharmacological intervention that can successfully increase mitochondrial respiration and result in memory enhancement and neuroprotection. Second, transcranial low-level light/laser therapy with near-infrared light is used to illustrate a photobiomodulation intervention with similar neurometabolic mechanisms of action as low-dose methylene blue. Finally, a nutrition intervention to improve mitochondrial respiration is proposed by increasing ketone bodies in the diet. The evidence discussed for each intervention supports a fundamental neurotherapeutic strategy based on improving oxidative energy metabolism while at the same time reducing the pro-oxidant tendencies of the nervous system. Targeting brain mitochondrial respiration with these three types of interventions is proposed as part of a holistic neurotherapeutic approach to improve brain energy metabolism and antioxidant defenses. This strategy represents a promising new bioenergetics direction for treatment of AD and other neuropsychological disorders featuring cognitive impairment and neurodegeneration.
本文聚焦于脑线粒体呼吸作为神经保护和认知增强的治疗靶点。我们提出，改善脑线粒体呼吸是阿尔茨海默病（AD）和其他与认知障碍和神经退行性变相关的疾病研究和治疗的重要未来方向。中心论点是，支持和改善脑线粒体呼吸是一种很有前途的神经治疗原则，它在 AD 以及广泛的神经心理疾病中有潜在的应用。我们提出了三种不同的干预方法来改善脑线粒体呼吸，基于（a）药理学、（b）光生物调节和（c）营养干预，并为每种干预类型提供了详细的例子。首先，低剂量 USP 亚甲蓝被描述为一种药理学干预方法，可以成功地增加线粒体呼吸，从而导致记忆增强和神经保护。其次，用近红外光进行经颅低水平光/激光治疗，说明了与低剂量亚甲蓝类似的神经代谢作用机制的光生物调节干预。最后，通过增加饮食中的酮体来提出改善线粒体呼吸的营养干预。讨论的每种干预措施的证据都支持了一种基于改善氧化能量代谢同时减少神经系统的促氧化剂倾向的基本神经治疗策略。通过这三种类型的干预来靶向脑线粒体呼吸，被提出作为改善大脑能量代谢和抗氧化防御的整体神经治疗方法的一部分。该策略代表了一种很有前途的新生物能量学方向，用于治疗 AD 和其他以认知障碍和神经退行性变为特征的神经心理疾病。
