" GALLY" International Biomedical Research Consulting LLC, 7733 Louis Pasteur Drive, #330. San Antonio, TX, 78229, USA.
Curr Med Chem. 2014;21(19):2208-17. doi: 10.2174/0929867321666131227161303.
Mitochondrial dysfunction plausibly underlies the aging-associated brain degeneration. Mitochondria play a pivotal role in cellular bioenergetics and cell-survival. Oxidative stress consequent to chronic hypoperfusion induces mitochondrial damage, which is implicated as the primary cause of cerebrovascular accidents (CVA) mediated Alzheimer's disease (AD). The mitochondrial function deteriorates with aging, and the mitochondrial damage correlates with increased intracellular production of oxidants and pro-oxidants. The prolonged oxidative stress and the resultant hypoperfusion in the brain tissues stimulate the expression of nitric oxide synthase (NOS) enzymes, which further drives the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ROS and RNS collectively contributes to the dysfunction of the blood-brain barrier (BBB) and damage to the brain parenchymal cells. Delineating the molecular mechanisms of these processes may provide clues for the novel therapeutic targets for CVA and AD patients.
线粒体功能障碍可能是与衰老相关的脑退行性变的基础。线粒体在细胞生物能量学和细胞存活中起着关键作用。慢性低灌注引起的氧化应激导致线粒体损伤，这被认为是阿尔茨海默病（AD）介导的脑血管意外（CVA）的主要原因。随着年龄的增长，线粒体功能恶化，线粒体损伤与细胞内氧化剂和促氧化剂的产生增加有关。脑组织中持续的氧化应激和由此导致的低灌注刺激一氧化氮合酶（NOS）酶的表达，进一步促使活性氧（ROS）和活性氮（RNS）的形成。ROS 和 RNS 共同导致血脑屏障（BBB）功能障碍和脑实质细胞损伤。阐明这些过程的分子机制可能为 CVA 和 AD 患者提供新的治疗靶点的线索。
