Molecular, Cellular, Behavioral Biology and Translational Research in Neurodegeneration
Our long-term goal is to understand the molecular and cellular mechanisms of neurodegeneration that causes human neurological disorders such as Parkinson’s, Huntington’s and Alzheimer’s diseases. Our mission is to translate our knowledge from basic research to the development of molecular diagnostics and therapeutics for neurological disorders. Our primary research interests encompass molecular and cellular pathways for autophagy-lysosome degradation, protein quality control (aggregate clearance), synaptic vesicle trafficking, neuroinflammation, and protein/lipid kinase signaling in neuropathogenesis.
Other Web Sites
Apoptosis/Cell Death, Autophagy, Axonal Growth and Degeneration, Human Genetics and Genetic Disorders, Knockout Mice, Lysosomes/endosome, Molecular Biology, Neuro-degeneration/protection, Parkinson's Disease, Protein Degradation, Protein Kinases, Protein Trafficking & Sorting, Synapses
Multi-Disciplinary Training Areas
Biophysics and Systems Pharmacology [BSP], Neuroscience [NEU]
- Autophagy-lysosome pathway as neuroprotection mechanism in the maintenance of axon and dendrite homeostasis and the clearance of protein aggregates, including polyQ expansion proteins (such as Huntingtin), tau and alpha-synuclein.
- The regulation of autophagy and endocytosis in neurons and neurodegeneration by PI3K-III lipid kinase complex proteins, including the modulators/adaptors: Beclin 1, Atg14L, URRAG, Rubicon and NRBF2; development of small compounds as modulators for PI3K-III activity and neuronal autophagy.
- Protein/lipid kinase and phosphatase in regulating synaptic vesicle trafficking and dysfunction in neurotransmission underlying Parkinson’s disease.
- The contribution of peripheral immune system and CNS glial cells to the neuroinflammation pathways underlying neurodegeneration mechanism in Parkinson’s disease and other human disorders.
- The molecular, cellular, and structural dissection of LRRK2 kinase in familial Parkinson’s disease; kinase inhibitor development as therapeutics to treat Parkinson’s disease.
- Genetic animal model development for human movement disorders and neurodegenerative diseases.
Lu J, He L, Behrends C, Araki M, Araki K, Jun Wang Q, Catanzaro JM, Friedman SL, Zong WX, Fiel MI, Li M, Yue Z. NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity. Nature communications 2014; 5.
Tang G, Gudsnuk K, Kuo SH, Cotrina ML, Rosoklija G, Sosunov A, Sonders MS, Kanter E, Castagna C, Yamamoto A, Yue Z, Arancio O, Peterson BS, Champagne F, Dwork AJ, Goldman J, Sulzer D. Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits. Neuron 2014 Sep; 83(5).
Friedman AK, Walsh JJ, Juarez B, Ku SM, Chaudhury D, Wang J, Li X, Dietz DM, Pan N, Vialou VF, Neve RL, Yue Z, Han MH. Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience. Science (New York, N.Y.) 2014 Apr; 344(6181).
Yue Z, Yang XW. Dangerous duet: LRRK2 and α-synuclein jam at CMA. Nature neuroscience 2013 Apr; 16(4).
Yamamoto A, Yue Z. Autophagy and its normal and pathogenic states in the brain. Annual review of neuroscience 2014; 37.
Yang Y, Coleman M, Zhang L, Zheng X, Yue Z. Autophagy in axonal and dendritic degeneration. Trends in neurosciences 2013 Jul; 36(7).
Sheng Z, Zhang S, Bustos D, Kleinheinz T, Le Pichon CE, Dominguez SL, Solanoy HO, Drummond J, Zhang X, Ding X, Cai F, Song Q, Li X, Yue Z, van der Brug MP, Burdick DJ, Gunzner-Toste J, Chen H, Liu X, Estrada AA, Sweeney ZK, Scearce-Levie K, Moffat JG, Kirkpatrick DS, Zhu H. Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations. Science translational medicine 2012 Dec; 4(164).
Steele JW, Lachenmayer ML, Ju S, Stock A, Liken J, Kim SH, Delgado LM, Alfaro IE, Bernales S, Verdile G, Bharadwaj P, Gupta V, Barr R, Friss A, Dolios G, Wang R, Ringe D, Fraser P, Westaway D, St George-Hyslop PH, Szabo P, Relkin NR, Buxbaum JD, Glabe CG, Protter AA, Martins RN, Ehrlich ME, Petsko GA, Yue Z, Gandy S. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model. Molecular psychiatry 2013 Aug; 18(8).
Friedman LG, Lachenmayer ML, Wang J, He L, Poulose SM, Komatsu M, Holstein GR, Yue Z. Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 2012 May; 32(22).
Yue Z, Lachenmayer ML. Genetic LRRK2 models of Parkinson's disease: Dissecting the pathogenic pathway and exploring clinical applications. Movement disorders : official journal of the Movement Disorder Society 2011 Jul; 26(8).
Zhong Y, Wang QJ, Li X, Chait BT, Heintz N, Yue Z. Distinct Regulation of Autophagic Activity by Novel Components Atg14L and Rubincon in Beclin 1-Vps34/phosphatidylinositol (PtdIns) 3-kinase complex. Nature Cell Biology 2009;.
McMahon J, Huang X, Yang J, Komatsu M, Yue Z, Qian J, Zhu X, Huang Y. Impaired autophagy in neurons after disinhibition of mammalian target of rapamycin and its contribution to epileptogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 2012 Nov; 32(45).
Arsov I, Li X, Matthews G, Coradin J, Hartmann B, Simon AK, Sealfon SC, Yue Z. BAC-mediated transgenic expression of fluorescent autophagic protein Beclin 1 reveals a role for Beclin 1 in lymphocyte development. Cell Death and Differentiation 2008; 15(9): 1385-1395.
Komatsu M, Waguri S, Koike M, Sou YS, Ueno T, Hara T, Mizushima N, Iwata J, Ezaki J, Murata S, Hamazaki J, Nishito Y, Iemura S, Natsume T, Yanagawa T, Uwayama J, Warabi E, Yoshida H, Ishii T, Yue Z, Uchiyama Y, Kominami E, Tanaka K. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 2007; 131(6): 1149-1163.
Ullman E, Fan Y, Stawowczyk M, Chen HM, Yue Z, Zong WX. Autophagy promotes necrosis in apoptosis-deficient cells in response to ER stress. Cell Death and Differentiation 2008 Feb; 15(2): 422-425.
Li X, Tan YC, Poulose S, Olanow CW, Huang XY, Yue Z. Leucine-Rich Repeat Kinase 2 (LRRK2)/PARK8 Possesses GTPase Activity That is Altered in Familial Parkinsons' Disease R1441C/G Mutants. Journal of Neurochemistry 2007; 103(1): 238-247.
Komatsu M, Wang Q, Holstein G, Kominami E, Chait BT, Tanaka K, Yue Z. Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration. Proc. Natl. Acad. Sci. USA 2007; 104(36): 14489-14494.
Tang G, Yue Z, Hagemann T, Messing A, Goldman JE. Expression of Alexander Disease-mutant GFAP Stimulates Autophagy through p38 MAPK and mTOR signaling Pathways. Human Molecular Genetics 2008; 17(11): 1540-1555.
Wang Q, Ding Y, Kolhz S, Mizushima N, Chait B, Zhong Y, Heintz N, Yue Z. Induction of autophagy in axonal dystrophy and degeneration. Journal of Neuroscience 2006; 26(31): 8057-8068.
Yue Z, Jin V, Yang C, Levine A, Heintz N. Beclin1, an autophagy gene essential for early embryonic development, is a haplo-insufficient tumor suppressor. Proc. Natl. Acad. Sci. USA 2003; 100(25): 15077-15082.
Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N. A 2) and Autophagy:S2 Glutamate Receptor (GluRSNovel Protein Complex linking the Implications for Neurodegeneration in Lurcher Mice. Neuron 2002; 35(9): 921-933.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Yue during 2016 and/or 2017. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
- Genentech, Inc.
- Pfizer Inc.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.
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