Mitochondrial dysfunction is a central protagonist of Alzheimer's disease (AD) pathogenesis. Mitochondrial dysfunction stems from various factors including mitochondrial DNA damage and oxidative stress from reactive oxygen species, membrane and ionic gradient destabilization, and interaction with toxic proteins such as amyloid beta (Aβ). Therapeutic drugs such as cholinesterase and glutamate inhibitors have proven to improve synaptic neurotransmitters, but do not address mitochondrial dysfunction. Researchers have demonstrated that oxidative damage may be reduced by increasing endogenous antioxidants, and/or increasing exogenous antioxidants such as vitamin C & E, beta-carotene and glutathione. Nonetheless, as AD pathology intensifies, endogenous antioxidants are overwhelmed, and exogenous antioxidants are unable to reach neuronal mitochondria as they are blocked by the blood brain barrier. Current therapeutic methods however include novel usage of lipophilic phosphonium cation bound to antioxidants, to effect neuronal mitochondria targeted activity. Mitochondria targeted MitoQ, MitoVitE, MitoTempo, MitoPBN and MCAT concentrate within mitochondria where they scavenge free-radicals, and augment mitochondrial dysfunction. Additional molecules include Szeto-Schiller (SS) peptides which target stability of the inner mitochondrial membrane, and DDQ molecule capable of improving bioenergetics and reduce mitochondrial fragmentation. This article discusses advantages and disadvantages of small molecules, their ability to mitigate Aβ induced damage, and ability to ameliorate synaptic dysfunction and cognitive loss.

线粒体功能障碍是阿尔茨海默氏病（AD）发病机理的主要角色。线粒体功能障碍源于多种因素，包括线粒体DNA损伤和活性氧的氧化应激，膜和离子梯度失稳以及与有毒蛋白质（如淀粉样蛋白β（Aβ））的相互作用。胆碱酯酶和谷氨酸抑制剂等治疗药物已被证明可以改善突触神经递质，但不能解决线粒体功能障碍。研究人员已经证明，可以通过增加内源性抗氧化剂和/或增加外源性抗氧化剂（例如维生素C和E，β-胡萝卜素和谷胱甘肽）来减少氧化损伤。但是，随着AD病理的加剧，内源性抗氧化剂不堪重负，外源性抗氧化剂无法到达神经元线粒体，因为它们被血脑屏障所阻断。然而，当前的治疗方法包括与抗氧化剂结合的亲脂性阳离子的新用途，以实现神经元线粒体靶向活性。线粒体靶向的MitoQ，MitoVitE，MitoTempo，MitoPBN和MCAT集中在线粒体中，它们清除自由基并加剧线粒体功能障碍。其他分子包括靶向线粒体内膜稳定性的Szeto-Schiller（SS）肽，以及能够改善生物能并减少线粒体断裂的DDQ分子。本文讨论了小分子的优缺点，它们减轻Aβ诱导的损伤的能力以及缓解突触功能障碍和认知丧失的能力。