Synaptic mitochondria are crucial for maintaining synaptic activity due to their high energy requirements, substantial calcium (Ca²⁺) fluctuation, and neurotransmitter release at the synapse. To provide a continuous energy supply, neurons use special mechanisms to transport and distribute healthy mitochondria to the synapse while eliminating the damaged mitochondria from the synapse. Along the neuron, mitochondrial membrane potential (ψ) gradient exists and is highest in the somal region. Lower ψ in the synaptic region renders mitochondria more vulnerable to oxidative stress-mediated damage. Secondly, mitochondria become susceptible to the release of cytochrome c, and mitochondrial DNA (mtDNA) is not shielded from the reactive oxygen species (ROS) by the histone proteins (unlike nuclear DNA), leading to activation of caspases and pronounced oxidative DNA base damage, which ultimately causes synaptic loss. Both synaptic mitochondrial dysfunction and synaptic failure are crucial factors responsible for Alzheimer’s disease (AD). Furthermore, amyloid beta (Aβ) and hyper-phosphorylated Tau, the two leading players of AD, exaggerate the disease-like pathological conditions by reducing the mitochondrial trafficking, blocking the bi-directional transport at the synapse, enhancing the mitochondrial fission via activating the mitochondrial fission proteins, enhancing the swelling of mitochondria by increasing the influx of water through mitochondrial permeability transition pore (mPTP) opening, as well as reduced ATP production by blocking the activity of complex I and complex IV. Mild cognitive impairment (MCI) is also associated with decline in cognitive ability caused by synaptic degradation. This review summarizes the challenges associated with the synaptic mitochondrial dysfunction linked to AD and MCI and the role of phytochemicals in restoring the synaptic activity and rendering neuroprotection in AD.

突触线粒体由于其高能量需求、大量钙 (Ca ²⁺ ) 波动和突触释放的神经递质，对于维持突触活动至关重要。为了提供持续的能量供应，神经元使用特殊的机制将健康的线粒体运输和分配到突触，同时从突触中消除受损的线粒体。沿着神经元，存在线粒体膜电位 (ψ) 梯度，并且在索马里区域最高。突触区 ψ 较低，使线粒体更容易受到氧化应激介导的损伤。其次，线粒体变得容易受到细胞色素c释放的影响，并且组蛋白（与核 DNA 不同）无法保护线粒体 DNA (mtDNA) 免受活性氧 (ROS) 的影响，导致半胱天冬酶激活和明显的氧化性 DNA 碱基损伤，最终导致突触损失。突触线粒体功能障碍和突触衰竭都是导致阿尔茨海默病（AD）的关键因素。此外，β淀粉样蛋白（Aβ）和过度磷酸化的Tau蛋白是AD的两个主要参与者，它们通过减少线粒体运输、阻断突触的双向运输、通过激活线粒体增强线粒体裂变来夸大疾病样病理状况。线粒体裂变蛋白，通过增加线粒体通透性转换孔 (mPTP) 开口的水流入来增强线粒体的肿胀，并通过阻断复合物 I 和复合物 IV 的活性来减少 ATP 的产生。轻度认知障碍（MCI）也与突触退化引起的认知能力下降有关。这篇综述总结了与 AD 和 MCI 相关的突触线粒体功能障碍相关的挑战，以及植物化学物质在恢复突触活性和提供 AD 神经保护方面的作用。