Pharmacology 514:
Current Topics in Pharmacology
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Current Topics in Pharmacology
Phcol 514
12:30 PM, Wednesday, December 1, 1999
Room T-530/530A HSC

Speaker: Sandra Bajjalieh
Topic: S'wonderful Synuclein--that you should cause PD

Many paths led to synuclein:

  1. Maroteaux L, Campanelli JT, and Scheller RH. (1988) Synuclein: A Neuron-Specific Protein Localized to the Nucleus and Presynaptic Nerve Terminal. J. Neurosci. 8:2804-2815.

  2. Iwai A, Masliah E, Yoshimoto M, Ge N, Flanagan L, Rohan de Silva HA, Kittel A, and Saltoh T. (1995) The Precursor Protein of Non-Ab Component of Alzheimer's Disease Amyloid is a Presynaptic Protein of the Central Nervous System. Neuron 14:467-475.

  3. George JM, Jin H, Woods WS, and Clayton DF. (1995) Characterization of a Novel Protein Regulated during the Critical Period for Song Learning in the Zebra Finch. Neuron 15:361-372.

  4. Ji H, Liu YE, Jia T, Wang M, Liu J, Xiao G, Joseph BK, Rosen C, and Shi YE. (1997) Identifcation of a Breast Cancer-specific Gene, BCSG1, by Direct Differential cDNA Sequencing. Cancer Research 57:759-764.

  5. Buchman VL, Adu J, Pinõn GP, Ninkina NN, and Davies AM. (1998) Persyn, a member of the synuclein family, influences neurofiliment network integrity. Nat. Neurosci. 1:101-103.

Mutations in synuclein are linked to neurodegenerative diseases:
  1. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di'lorio G, Golbe LI, and Nussbaum RL. (1997) Mutation in the a-Synuclein Gene Identified in Families with Parkinson's Disease. Science 276:2045-2047.

  2. Galvin JE, Uryu K, Lee VM-Y, Trojanowski JQ. (1999) Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains a-, b-, and g-synuclein. Proc. Natl. Acad. Sci. USA 96:13450-13455.

  3. Narhi L, Wood SJ, Steavenson S, Jiang Y, Wu GM, Anafi D, kaufman SA, Martin F, Sitney K, Denis P, Louis J-C, Wypych J, Biere AL, and Citron M. (1999) Both Familial Parkinson's Disease Mutations Accelerate a-Synuclein Aggregation. J. Biol. Chem. 274:9843-9846.

  4. Wood SJ, Wypych J, Steavenson S, Louis J-C, Citron M, and Biere AL. (1999) a-Synuclein Fibrillogenesis is Nucleation-dependent. J. Biol. Chem. 274:19509-19512.

Clues to Synuclein's Function:
  1. Weinreb PH, Zhen W, Poon AW, Conway KA, and Lansbury PT. (1996) NACP, A Protein Implicated in Alzheimer's Disease and Learning, is Natively Unfolded. Biochemistry 35:13709-13715.

  2. Davidson WS, Jonas A, Clayton DF, and George JM. (1998) Stabilization of a-Synuclein Secondary Structure upon Binding to Synthetic Membranes. J. Biol. Chem. 273:9443-9449.

  3. Jensen PH, Nielsen MS, Jakes R, Dotti CG, and Goedert M. (1998) Binding of a-Synuclein to Brain Vesicles is Abolished by Familial Parkinson's Disease Mutation. J. Biol. Chem. 273:26292-26294.

  4. Jenco JM, Rawlingson A, Daniels B, and Morris AJ. (1998) Regulation of Phospholipase D2: Selective Inhibition of Mammalian Phospholipase D Isoenzymes by a- and b-Synucleins. Biochemistry 37:4901-4909.

  5. Jia T, Liu YE, Liu J, and Shi YE. (1999) Stimulation of Breast Cancer Invasion and Metastasis by Synuclein g1. Cancer Research 59:742-747.

  6. Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, and Wolozin B. (1999) a-Synuclein Shares Physical and Functional Homology with 14-3-3 Proteins. J. Neurosci. 19:5782-5791.

  7. Engelender S, Kaminsky Z, Guo X, Sharp AH, Amaravi RK, Kleiderlein JJ, Margolis RL, Troncoso JC, Lanahan AA, Worley PF, Dawson VL, Dawson TM, and Ross CA. (1999) Synphilin-1 associates with a-synuclein and promotes the formulation of cytosolic inclusions. Nat. Genetics 22110-114.

Reviews:
  1. Clayton DF and George JM. (1998) The synucleins: a familiy of proteins involvedin synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci. 21:249-254.

  2. Goedert M, Spillantini MG, and Davies SW. (1998) Filamentous nerve cell inclusions in neurodegenerative diseases. Curr. Opin. Neurobio. 8:619-632.


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