Yan Lab

Lab Members

Research Interests

Research in my laboratory focuses on investigating the cellular and molecular mechanisms of cellular stress and survival in neurodegenerative disorders relevant to Alzheimer’s disease (AD), multiple sclerosis, and diabetes. We have first identified the specific cellular targets and mitochondrial protein for amyloid-beta peptide (Aβ) and diabetes induced mitochondrial and synaptic injury.  We developed several novel transgenic human disease mouse models relevant to AD, diabetes, and aging to test mitochondria-mediated signaling , which contributes to synaptic and cognitive dysfunction. Dr. Yan and her research team are the major group investigating these paradigms. Mitochondrial dysfunction is a hallmark of AD. We discovered that Aβ progressively accumulated in mitochondria of brains from AD patients and transgenic AD-type mouse model. Accumulation of Aβ in mitochondria was associated with mitochondrial dysfunction. These studies provide new insights into mechanisms of Aβ-mediated mitochondrial toxicity causing neuronal damage relevant to AD and open new avenue for treatment of AD. We are identifying proteins which interact with mitochondrial Aβ in transgenic AD-type mouse models implicating for pathogenesis of AD.  In addition, we are focusing on cellular and molecular mechanisms underlying ischemia-induced cerebral injury, and autoimmune disease such as EAE (experimental autoimmune encephalomyelitis) animal model relevant to multiple sclerosis.

Selected Recent Publications

  • Yan, SD, Yan, S-F., Chen, X., Fu, J., Chen, M., Kuppusamy, P., Smith, M.A., Perry., G., Godman,G.C., Nawroth, P., Zweier, J.L., and Stern, D. Non-enzymatically glycated tau in Alzheimer’s disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid ß-peptide. Nature Medicine, 1(7):693-699, 1995
  • Yan SD, Chen X, fu J, Chen M, Zhu H, Roher A, Slattery T, Nagashima M, Morser J, Migheli A, Nawroth P, Goodmand G, Stern D, and Schmidt AM. RAGE in Alzheimer’s disease: a receptor mediating amyloid-ß peptide-induced oxidant stress and neurotoxicity, and microglial activation. Nature, 382:685 691, 1996.
  • Yan SD, Fu J., Soto C., Chen X., Zhu H., Al-Mohanna, F., Collison K., Zhu A., Stern E., Saido T., Tohyama, M., Ogawa, S., Roher, A and Stern, D. ERAB: an intracellular protein that binds amyloid-ß peptide and mediates neurotoxicity in Alzheimer’s disease. Nature 389:689-695, 1997.
  • Yan SD, Zhu H, Fu J, Yan S-F, Roher A, Tourtellotte W, Rajavashisth T, Chen X, Godman CG, Stern D and Schmidt AM: Amyloid-ß peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A 94:5296-5301,1997.
  • Yan, SD, Zhu, H., Zhu, A., Golabek, A., Roher, A., Yu, J., Soto, C., Schmidt, A-M., Stern, D., and Kindy, M. Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis. 6:643:651 Nature Medicine, 2000.
  • Yan SD, Wu ZY, Zhang HP, Furtado G, Chen X, Yan SF, Chris B , Stern A, LaFaille J, Chess L, Stern D,and Jiang H. Suppression of experimental autoimmune encephalitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. Nature Medicine 9(3):287-93, 2003
  • Deane R, Yan SD, Wu Z, Sagare A, Davis J, Hamm K, Xu f, Parisi M, LaRue B, Xu HW, Spijkers P, Guo H, Song X, Lenting PJ, Van Nostrand WE, and ZlokovicBV. et al., RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nature Medicine Jul;9(7):907-13, 2003.
  • Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang, N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SD, Wu H. (2004) ABAD Directly Links Aß to Mitochondrial Toxicity in Alzheimer's Disease. Science 2004 304: 448-452. Faculty of 1000 Top 10 Neuroscience
  • Arancio O, Zhang HP, Chen X, Lin C, Trinchese F, Puzzo D, Liu S, Hegde A, Yan SF, Stern A, Luddy JS, Lue LF, Walker DG, Roher A, Buttini M, Mucke L, Li W, Schmidt AM, Kindy M, Hyslop PA, Stern DM, Yan SS. RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. EMBO J. 2004 Sep 30:1-10. Faculty of 1000 Top 10 Neuroscience.
  • Casperson C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JW, Xu HW, Stern D, McKhann G, Yan SD. Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease FASEB 2005:19: 2040-2063 FASEB J. 2005 Dec;19(14):2040-1. Epub 2005 Oct 6.
  • Takuma K, Yao J, Huang J, Luddy J, Trillar AC, Chen X, Arancio O, Yan SD. ABAD enhances Aß-induced cell stress via mitochondrial dysfunction. FASB J. express article, published online January 21, 2005.
  • Chen JX and Yan SD. Amyloid-beta-induced mitochondrial dysfunction. J Alzheimer’s Disease. 2007 Sep: 12(2):177-84.
  • Chen JX and Yan SD. Pathogenic role of mitochondrial amyloid- peptide. Exp Rev Neurother November 2007, Vol. 7, No. 11, Pages 1499-1516
  • Chen X, walker DG, Schmidt AM, Arancio O, Lue LF, Yan SD. RAGE: a potential target for Abeta-mediated cellular perturbation in Alzheimer's disease. Curr Mol Med. 2007 Dec;7(8):735-42.
  • Chen X, Stern D, and Yan SD. Cellular targets of amyloid beta peptide: potential roles in neuronal cell stress and toxicity. Chapter 11, Neurobiology of Alzheimer’s disease (Molecular and cellular biology series), third edition, Oxford publication, 2007. p227-244.
  • Du H, Guo L, Fang F, Chen D, Sosunov AA, Mckhann GM, Yan Y, Wang C, Zhang H, Molkentine JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature Medicine. 2008 Oct;14(10):1097-105. Epub 2008 Sep 21. PMID: 18806802, Faculty 1000 of Biology.
  • Origlia N, Righi M, Capsoni S, Cattaneo A, Fang F, Stern DM, Chen JX, Schmidt AM, Arancio O, Yan SD, Domenici L. (co-corresponding author) Receptor for Advanced Glycation Endproducts (RAGE)-dependent activation of p38 Mitogen-Activated Protein Kinase contributes to amyloid β-mediated cortical synaptic dysfunction. J. Neurosci. 2008 Mar 26;28:3521-3530.
  • Du H, Guo L, Zhang W, Rydzewska M, Yan S: Cyclophilin D deficiency improves mitochondrial function and learning/memory in aging Alzheimer disease mouse model. Neurobiol Aging 2009, April 10. PMID:19362755.
  • Takuma K, Fang F, Yan S, Zhang WS, Fukuzaki E, Du H, Sosunov A, McKhann G, Funatsu Y, Nakamichi N, Nagai T, Mizoguchi H, Ibi D, Hori O, Ogawa S, Stern D, Yamada K, and Yan SS. RAGE-mediated signaling contributes to intraneuronal transport of amyloid-β and neuronal dysfunction. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20021-6. Epub 2009 Nov 9. Faculty 1000 Medicine
  • Du H, Yan SS: Mitochondrial permeability transition pore in Alzheimer's disease: Cyclophilin D and amyloid beta. Biochim Biophys Acta. 2010 Jan;1802(1):198-204. Epub 2009 Jul 16.
  • Origlia N, Capsoni S, Cattaneo A, Fang F, Arancio O, Yan SD, Domenici L. Abeta-dependent inhibition of LTP in different intra-cortical circuits of the visual cortex: the role of RAGE. J Alzheimers Dis. 2009, May; 17(1):59-68.
  • Origlia N, Arancio O, Domenici L, Yan SS. MAPK, beta-amyloid and synaptic dysfunction: the role of RAGE. Expert Rev Neurother. 2009 Nov:9(11):1635-45.
  • Du H, Yan SS: Mitochondrial permeability transition pore in Alzheimer's disease: Cyclophilin D and amyloid beta. Biochim Biophys Acta. 2010 Jan;1802(1):198-204. Epub 2009 Jul 16.
  • Fang F , Lue LF, Walker DG , Xu HW, Luddy J, Chen D, Schmidt A, Stern DM, Arancio O, Chen JX, Yan SS. RAGE-dependent signaling in microglia contributes to neuroinflammation, Aß accumulation, and impaired learning/memory in a mouse model of Alzheimer’s disease. FASEB J. 2010 Apr;24(4):1043-55. Epub 2009 Nov 11.
  • Xu HW, Wu ZY, Fang F, Guo L, Chen D, Chen JX, Stern D, Taylor G, Chess L, Jiang H, Yan SS. Blockade of LRG-47 (Irgm1) promotes apoptosis and suppresses induction of experimental autoimmune encephalomyelitis. FASEB J. 2010 May;24(5):1583-92. Epub 2010 Jan 7.
  • Du H, Yan SS: Mitochondrial medicine for neurodegenerative diseases. Int J Biochem Cell Biol. 2010 Jan 12. [Epub ahead of print]
  • Origlia N, Bonadonna C, Rosellini A, Leznik E, Arancio O, Yan SS, Domenici L. Microglial RAGE-dependent signal pathway drives Aβ-induced synaptic depression and long-term depression impairment in entorhinal cortex. The Journal of Neuroscience, August 25, 2010, 30(4): 11414-11425.
  • Chen JX, Yan SS: Role of mitochondrial amyloid-beta in Alzheimer’s disease. J Alzheimers Disease 2010:20 Suppl:S560-78.
  • Du H, Yan SS. Unlocking the Door to Neuronal Woes in Alzheimer’s Disease: Aβ and Mitochondrial Permeability Transition Pore. Pharmaceuticals 2010, 3, 1936-1948; doi:10.3390/ph3061936
  • Du H, Guo L, Yan S, Sosunov AA, Mckhann GM, Yan SS. Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proc Natl Acad Sci U S A. 2010, Oct 26;107(43):18670-5. Epub 2010 Oct 11.

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