蛋白质的错误折叠参与了很多神经退行性疾病（如：阿尔茨海默氏症，帕金森氏症，亨廷顿症和脊髓侧索硬化症等）中的细胞凋亡过程。本实验室的研究集中在热休克蛋白家族对蛋白错误折叠的修复作用和对细胞凋亡的调节作用上。

    神经肽受体与经典兴奋性/抑制性神经递质受体有复杂的交互作用，影响着痛觉，学习记忆，神经元凋亡等重要通路。本实验室的研究集中在甘丙肽对细胞凋亡的影响以及对AMPA受体在膜上转运的作用上。

Research Description:

The main research interests in our lab include: involvement of signaling pathways in Alzheimer’s disease, mechanisms of neuronal apoptosis in neurodegenerative diseases and interactions of neuropeptide receptors and excitatory/inhibitory receptors.

One of the most significant pathological markers of Alzheimer’s disease (AD) is amyloid deposits. Whether amyloid is the definite cause of AD and how it may contribute to AD progression are still controversial. Taking the advantage of human primary neuron model to study human diseases, we are interested in how amyloid beta, especially intracellular amyloid beta induces neuronal death and how intracellular amyloid beta metabolizes and gets degraded.

Protein misfolding is shown to be involved in many neurodegenerative diseases, such as AD, Parkinson’s disease, Huntington disease and ALS. Our lab is interested in how heat shock protein family regulates correction and degradation of misfolded proteins, and in case that the misfolded proteins are not able to rescue, induces apoptosis.

Interactions of neuropeptide receptors and excitatory/inhibitory receptors have important implications in pain regulation, learning/memory and apoptosis. We are now focusing on the effects of galanin on neuronal cell death and AMPA receptor trafficking.

实验室网页：http://www.bio.pku.edu.cn/lab/neurosci/index.html

1. Guo H, Petrin D, Zhang Y, Bergeron C, Goodyer C and LeBlanc A. Caspase-1 activation of caspase-6 in human apoptotic neurons. 2006, Cell Death Differ, 13: 285-292.

2. Roucou X, Giannopoulos PN, Zhang Y, Jodoin J, Goodyer C and LeBlanc A. Cellular prion protein inhibits proapoptitic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells. 2005, Cell Death Differ, 12: 783-795.

3. Zhang Y, Beitel L, Goodyer C, Trifiro M and LeBlanc A. Estrogen and androgen protect against intracellular amyloid b toxicity. 2004, J Neurosci, 24: 5315-5321.

4. Tounekti O, Zhang Y, Goodyer C and LeBlanc A. Caspase inhibitory factor is mediated by a cysteinyl protease activity. 2004, J Neurochem, 89: 561-568.

5. Roucou X, Gou Q, Zhang Y, Bounhar Y, Goodyer C and LeBlanc A. Cytosolic PrP protects against Bax-mediated cell death in human neurons. 2003, J Biol Chem, 278: 40877-40881.

6. Zhang Y, Guo Y, Bounhar Y, Roucou X, Goodyer C and LeBlanc A. p75NTR protects against extracellular amyloid b toxicity in human neurons. 2003, J Neurosci. 23: 7385-7394.

7. Zhang Y, McLauglin R, Vereker E, Goodyer C and LeBlanc A. Selectively cytotoxicty of intracellular amyloid b peptide1-42 through p53 and Bax in cultured primary human neurons. 2002, J Cell Biol, 156: 519-529.

8. Zhang Y, Tounekti O, Akerman B, Goodyer C and LeBlanc A. 17-b-estradiol induces an inhibitor of active caspases. 2001, J Neurosci, 21: RC176, 1-6.

9. Bounhar Y, Zhang Y, Papasopulos M, Turcotte B, Goodyer C and leBlanc A. Prion protein protects human neurons against Bax-mediated cell death. 2001, J Biol Chem, 276: 39145-39149.

10 Zhang Y, Goodyer C and LeBlanc A. Selective and protracted apoptosis in human primary neurons microinjected with active caspase-3, -6, -7 and –8. 2000, J Neurosci, 20: 8384-8389.

综述
Reviews
Zhang Y, Chen Q and Yu L. Morphine: a protective or destructive role in neurons? Neuroscientist, 2008, in press.

Li M, Chen L, Lee D, Yu L and Zhang Y. The Role of Intracellular Amyloid β in Alzheimer’s Disease. Prog Neurobiol, 2007, 83: 131-139.

Zhang Y and Yu L. Recent progress in the study of intracellular toxicity of amyloid beta peptide in Alzheimer's disease. Prog Nat Sci. 2007, 17: 233-236.

Zhang Y and LeBlanc A. Microinjection of proteins, peptides and genes in human neuronal apoptosis study. In: Neuromethods, volume 37: Apoptosis Techniques and Protocols, 2nd Edition. Humana Press, Totowa, New Jersy, USA. 2002, pp.83-106.