J of Neurosci., 郑强和谢佐平实验室
Acute Impairment of Mitochondrial Trafficking by beta-Amyloid Peptides in Hippocampal Neurons
Yanfang Rui,1 * Priyanka Tiwari,2 * Zuoping Xie,1 and James Q. Zheng2
1Department of Biological Science and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing, China 100084, and 2Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854
Defects in axonal transport are often associated with a wide variety of neurological diseases including Alzheimer's disease (AD). beta-Amyloid (Abeta) is a major component of neuritic plaques associated with pathological conditions of AD brains. Here, we report that a brief exposure of cultured hippocampal neurons to Abeta molecules resulted in rapid and severe impairment of mitochondrial transport without inducing apparent cell death and significant morphological changes. Such acute inhibition of mitochondrial transport was not associated with a disruption of mitochondria potential nor involved aberrant cytoskeletal changes. Abeta also did not elicit significant Ca2+ signaling to affect mitochondrial trafficking. However, stimulation of protein kinase A (PKA) by forskolin, cAMP analogs, or neuropeptides effectively alleviated the impairment. We also show that Abeta inhibited mitochondrial transport by acting through glycogen synthase kinase 3beta (GSK3beta). Given that mitochondria are crucial organelles for many cellular functions and survival, our findings thus identify an important acute action of Abeta molecules on nerve cells that could potentially contribute to various abnormalities of neuronal functions under AD conditions. Manipulation of GSK3beta and PKA activities may represent a key approach for preventing and alleviating Abeta cytotoxicity and AD pathological conditions.
Key words: Abetapeptide; Alzheimer's disease; signal transduction; actin; calcium; cAMP; transport
【 在 illl (llli) 的大作中提到: 】
: 恭喜芮师姐，first author