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Gerstmann syndrome

Gerstmann syndrome is a neurological disorder characterized by four primary symptoms: more...

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  1. Dysgraphia/agraphia
  2. Dyscalculia/acalculia
  3. Finger agnosia
  4. Left-right disorientation

In adults, the syndrome may occur after a stroke or in association with damage to the parietal lobe. In addition to exhibiting the above symptoms, many adults also experience aphasia, which is a difficulty in expressing oneself when speaking, in understanding speech, or in reading and writing.

There are few reports of the syndrome, sometimes called developmental Gerstmann syndrome, in children. The cause is not known. Most cases are identified when children reach school age, a time when they are challenged with writing and math exercises. Generally, children with the disorder exhibit poor handwriting and spelling skills, and difficulty with math functions, including adding, subtracting, multiplying, and dividing. An inability to differentiate right from left and to discriminate among individual fingers may also be apparent. In addition to the four primary symptoms, many children also suffer from constructional apraxia, an inability to copy simple drawings. Frequently, there is also an impairment in reading. Children with a high level of intellectual functioning as well as those with brain damage may be affected with the disorder.

There is no cure for Gerstmann syndrome. Treatment is symptomatic and supportive. Occupational and speech therapies may help diminish the dysgraphia and apraxia. In addition, calculators and word processors may help school children cope with the symptoms of the disorder.

In adults, many of the symptoms diminish over time. Although it has been suggested that in children symptoms may diminish over time, it appears likely that most children probably do not overcome their deficits, but learn to adjust to them.

The National Institute of Neurological Disorders and Stroke (NINDS) supports research on disorders that result from damage to the brain such as dysgraphia. The NINDS and other components of the National Institutes of Health also support research on learning disabilities. Current research avenues focus on developing techniques to diagnose and treat learning disabilities and increase understanding of the biological basis of them.

This disorder is often associated with brain lesions in the dominant (usually left) side of the angular and supramarginal gyri near the temporal and parietal lobe junction.

It should not be confused with Gerstmann-Straussler syndrome, which is a transmissible spongiform encephalopathy.


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Computational studies on prion proteins: Effect of Ala(117)-->Val mutation
From Biophysical Journal, 5/1/02 by Okimoto, Noriaki

ABSTRACT Molecular dynamics calculations demonstrated the conformational change in the prion protein due to Ala^sup 117^-->Val mutation, which is related to Gerstmann-Straussler-Sheinker disease, one of the familial prion diseases. Three kinds of model structures of human and mouse prion proteins were examined: (model 1) nuclear magnetic resonance structures of human prion protein HuPrP (125-228) and mouse prion protein MoPrP (124-224), each having a globular domain consisting of three a-helices and an antiparallel beta-sheet; (model 2) extra peptides including Ala^sup 117^ (109-124 in HuPrP and 109-123 in MoPrP) plus the nuclear magnetic resonance structures of model 1; and (model 3) extra peptides including Val"' 17 (109-124 in HuPrP and 109-123 in MoPrP) plus the nuclear magnetic resonance structures of model 1. The results of molecular dynamics calculations indicated that the globular domains of models 1 and 2 were stable and that the extra peptide in model 2 tended to form a new alpha-helix. On the other hand, the globular domain of model 3 was unstable, and the 1-sheet region increased especially in HuPrP.


Prion diseases are manifested as familial infections or sporadic diseases, and they cause neurodegenerative disorders such as kuru, Creutzfeldt-Jacob disease, Gerstmann-Straussler-Sheinker syndrome (GSS), and fatal familial insomnia in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals (Prusiner and DeArmond, 1994). These disorders are thought to be caused by the transformation of a normal prion protein (PrP^sup C^) into an abnormal prion protein (PrP^sup C^), which accumulates in plaques in the brain (Borchelt et al., 1990). The replication of PrP^sup C^ is thought to occur through interaction between PrP^sup C^ and PrP^sup C^ with the assistance of a protein X acting as a chaperon (Telling et al., 1995). PrP^sup c^ has one disulfide bridge (Fig. 1) and is anchored to the cell membrane via a glycosyl phosphatidyl inositol anchor (Stahl et al., 1987, 1992). The important point is that no chemical difference between PrP^sup C^ and PrP^sup SC^ has been identified (Stahl et al., 1993). However, experiments using circulator dichroism and Fourier-transform infrared analyses have shown that PrPc has a low beta-sheet content (~3%) and is sensitive to proteases, whereas PrP^sup SC^ has a high beta-sheet content (~30%) and is protease-resistant (Pan et al., 1993; Safar et al., 1993). Recently, nuclear magnetic resonance (NMR) experiments have revealed the three-dimensional structures of mouse prion protein MoPrP (Riek et al., 1996, 1997, 1998), Syrian hamster prion protein ShPrP (Donne et al., 1997; Liu et al., 1999; James et al., 1997), bovine prion protein (Garcia et al., 2000), and human prion protein HuPrP (Zahn et al., 2000), all of which correspond to PrPc. These structural data have indicated that the N-terminal region (~125) is flexible and that the C-terminal region containing the globular domain (125-228) is rigid. The globular domain consists of three alpha-helices and a short antiparalell beta-sheet (Fig. 2).

Most cases of human prion diseases occur spontaneously by unknown causes. However, familial prion diseases such as GSS, fatal familial insomnia, and Creutzfeldt-Jacob disease are related to distinct point mutants within the human gene of PrPc (PRNP) (Hsiao et al., 1989; Kretzschmar 1993). Point mutations in the PRNP gene are seen in 102, 105, 117, 145, 198, and 217 in GSS and 178, 200, and 210 in most cases of Creutzfeldt-Jacob disease. Some mutations related to GSS occur only in a few families (Tateishi et al., 1990; Hsiao et al., 1991; Mastrianni et al., 1995), e.g., P102L mutation was detected in more than 30 families, whereas Ala^sup 117^-->Val mutation was detected in only three families (Trenchant et al., 1997). It is interesting that Ala^sup 117^-Val mutation requires two changes in the genetic code to generate an amino acid change. It is known that Ala^sup 117^--> Val mutation is coupled with Val , which is Met/Val heterozygous at codon 129 (Trenchant et al., 1997). Other experiments on peptides with Ala^sup 117^-->Val mutation have shown that the beta-sheet region tended to increase (Brown 2000). In the current work, focusing on the Ala^sup 117^-Val mutation, we tried to elucidate the correlation between Ala^sup 117^-->Val mutation and prion protein (PrP) structure using molecular dynamics (MD) and quantum chemical calculations. CONCLUSIONS

We provide the following conclusion from this study. Ala^sup 117^--> Val mutation deforms the structures of the globular domains on HuPrP and MoPrP. Especially in HuPrP containing Val 17, the extension of the P-sheet and the collapse of HI occur. PrPc containing Ala^sup 117^ tended to form a-helix in the extra peptide chain (109-124 in HuPrP and 109-123 in MoPrP). The extra peptide chain 119-122) containing Val^sup 117^ takes high electron distribution in some frontier molecular orbitals and had a high reactivity. These would be the driving force for the flexible motion of the N-terminal region of the mutant structure.

This work was supported by the super computer VPP700 in RIKEN. The computations were also carried out by the DRIA System at the Graduate School of Pharmaceutical Sciences, Chiba University.


Berendsen, H. J. C., J. P. M. Postma, W. F. van Gunsteren, A. DiNola, and J. R. Haak. 1984. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81:3684-3690.

Berman, H. M., J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E. Bourne. 2000. The Protein Data Bank. Nucleic Acids Res. 28:235-242.

Borchelt, D. R., M. Scott, A. Taraboulos, N. Stahl, and S. B. Prusiner. 1990. Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells. J. Cell. Biol. 110:743-752.

Brown, D. R. 2000. Altered toxicity of the prion protein peptide PrP 106-126 carrying the Ala"'*Val mutation. Biochem. J. 346:785-791. Case, D. A., D. A. Pearlman, J. W. Caldwell, T. E. Cheatham, HI, W. S.

Ross, C. L. Simmerling, T. A. Darden, K. M. Merz, R. V. Stanton, A. L. Cheng, J. J. Vincent, M. Crowley, D. M. Ferguson, R. J. Radmer, G. L. Seibel, U. C. Singh, P. K. Weiner, and P. A. Kollman. 1997. AMBER 5. University of California, San Francisco, CA.

Cornell, W. D., P. Cieplak, C. I. Bayly, 1. R. Gould, K. M. Merz, Jr., D. M. Ferguson, D. C. Spellmeyer, T. Fox, J. W. Caldwell, and P. A. Kollman. 1995. A second generation forth field for the simulation of proteins and nucleic acids. J. Am. Chem. Soc. 117:5179-5197.

Donne, D. G., J. H. Viles, D. Groth, I. Mehlhorn, T. L. James, F. E. Cohen, S. B. Prusiner, P. E. Wright, and H. J. Dyson. 1997. Structure of the recombinant full-length hamster prion protein PrP (29-231): the N terminus is highly flexible. Proc. Natl. Acad. Sci. U. S. A. 94: 13452-13457.

Garcia, L. F., R., Zahn., R., Riek and, K., Wuthrich. 2000. NMR structure of the bovine prion protein. Proc. Natl. Acad. Sci. U. S. A. 97: 8334-8339.

Hanan, E., 0. Goren, M. Eshkenazy, and B. Solomon. 2001. Immunomodulation of the human prion peptide 106-126 aggregation. Biochem. Biophys. Res. Commun. 280:115-120.

Hsiao, K., H. F. Baker, T. J. Crow, M. Pointer, F. Owen, J. D. Terwilliger, D. Westaway, J. Ott, and S. B. Prusiner. 1989. Linkage of a prion protein missense variant to Gerstmann-Straussler syndrome. Nature. 338: 342-345.

Hsiao, K. K., C. Cass, G. D. Schellenberg, T. Bird, E. Devine-Gage, H. Wisniewski, and S. B. Prusiner. 1991. A prion protein variant in a family with the telencephalic form of Gerstmann-Strausser-Scheinker syndrome. Neurology. 41:681-684.

James, T. L., H. Liu, N. B. Ulyanov, S. Farr-Jones, H. Zhang, D. G. Donne, K. Kaneko, D. Groth, I. Mehlhorn, S. B. Prusiner, and F. E. Cohen. 1997. Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform. Proc. Natl. Acad. Sci. U. S. A. 94:10086-10091.

Jorgensen, W. L., J. Chandrasekhar, and J. D. Madura. 1983. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79:926-935.

Koradi, R., M. Billeter, and K. Wuthrich. 1996. MOLMOL: a program for display and analysis of macromolecular structure. J. Mol. Graphics. 4:51-55.

Korth, C., B. Stierli, P. Streit, M. Moser, 0. Schaller, R. Fischer, W. Schulz-Schaeffer, H. Kretzschmar, A. Raeber, U. Braun, F. Ebrensperger, S. Hornemann, R, Glockshuber R. Riek, M. Billeter, K. Wuthrich, and B. Oesch. 1997. Prion (PrP "c)-specific epitope defined by a monoclonal antibody. Nature. 390:74-77.

Kretzschmar, H. A. 1993. Human prion diseases (spongiform encephalopathies). Arch. Virl. Suppl. 7:261-293.

Laskowski, R. A., M. W. MacArthur, D. S. Moss, and J. M. Thornton. 1993. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Cryst. 26:283-291.

Liemann, S., and R. Glockshuber, R. 1999. Influence of amino acid substitutions related to inherited human prion diseases on the thermodynamic stability of the cellular prion protein. Biochemistry. 38: 3258-3267.

Liu, H., S. Farr-Jones, N. B. Ulyanov, M. Llinas, S. Marqusee, D. Groth, F. E. Cohen, S. B. Prusiner, and T. L. James. 1999. Solution structure of

Syrian hamster prion protein rPrP (29-231). Biochemistry. 38: 5362-5377.

Mastrianni, J. A., M. T. Curtis, J. C. Oberholtzer, M. M. Da Costa, S. DeAr-mond, S. B. Prusiner, and J. Y. Garbem. 1995. Prion disease (PrP -Ala"-Val) presenting with ataxia instead of dementia. Neurology. 45:2042-2050.

Morrissey, M. P., and E. I. Shakhnovich. 1999. Evidence for the role of PrP` helix I in the hydrophilic seeding of prion aggregates. Proc. Natl. Acad. Sci. U. S. A. 96:11293-11298.

Narumi, T., A. Kawai, and T. Koishi. 2001. An 8.61 Tflop/s Molecular Dynamics Simulation for NaCl with a Special-Purpose Computer: MDM. In Proc. SC2001 (CDROM). Assoc. Comp. Machinery, New York.

Pan, K. M., M. Baldwin, J. Nguyen, M. Gasset, A. Serban, D. Groth, I. Mehlehorn, Z. Huang, R. J. Fletterick, F. E. Cohen, and S. B. Prusiner. 1993. Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc. Natl. Acad. Sci. YJ. S. A. 90:10962-10966.

Prusiner, S. B., and S. DeArmond. 1994. Biology and genetics of prion diseases. Annu. Rev. Neurosci. 17:311-319.

Riek, R., S. Hornemann, G. Wider, M. Billeter, R. Glockshuber, and K. Wuthrich. 1996. NMR structure of the mouse prion protein domain PrP (121-231). Nature. 382:180-182.

Rick, R., S. Hornemann, G. Wider, R. Glockshuber, and K. Wuthrich. 1997. NMR characterization of the full-length recombinant murine prion protein, mPrP (23-231). FEBS Lett. 413:282-288.

Riek, R., G. Wider, M. Billeter, S. Hornemann, R. Glockshuber, and K. Wuthrich. 1998. Prion protein NMR structure and familial human spongiform encephalopathies. Proc. Natl. Acad. Sci. U. S. A. 95: 11667-11672.

Ryckaert, J. P., G. Ciccotti, and H. J. C. Berendsen. 1977. Numerical integration of the Cartesian equations of proteins and nucleic acids. J. Comput. Phys. 23:327-341.

Safar, J., P. P. Roller, D. C. Gajdusek, and C. J. Gibbs. 1993. Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity. Protein Sci. 2:2206-2216.

Stahl, N., M. A. Baldwin, R. Hecker, K. M. Pan, A. L. Burlingame, and S. B. Prusiner. 1992. Glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid. Biochemistry. 31:5043-5053.

Stahl, N., M. A. Baldwin, D. B. Teplow, L. Hood, B. W. Gibson, A. L. Burlingame, and S. B. Prusiner. 1993. Structural studies of the scrapie prion protein using mass. Biochemistry. 32:1991-2002.

Stahl, N., D. R. Borchelt, K. Hsiao, and S. B. Prusiner. 1987. Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell. 51:229-240. Stewart, J. J. P. 1989a. Optimization of parameters for semi-empirical methods I-methods. J. Comp. Chem. 10:209-220.

Stewart, J. J. P. 1989b. Optimization of parameters for semi-empirical methods II-applications. J. Comp. Chem. 10:221-264.

Stewart, J. J. P., and J. Frank. 1990. Mopac Manual, sixth edition: A General Molecular Orbital Package. Frank J. Seiler Research Laboratory, U.S. Air Force Academy, Colorado Springs, CO.

Tateishi, J., T. Kitamoto, K. Dohura, Y. Sakaki, G. Steinmets, C. Tranchant, J. M. Waiter, and N. Heldt. 1990. Immunochemical, molecular genetic, and transmission studies on a case of Gerstmann-StrausslerSheinker syndrome. Neurology. 40:1578-1581.

Telling, G. C., M. Scott, J. Mastrianni, R. Gabizon, M. Torchia, F. E. Cohen, S. J. DeArmond, N. Stahl, and S. B. Prusiner. 1995. Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell. 83:79-99.

Tranchant, C., N. Sergeant, A. Wattez, M. Mohr, J. M. Warter, and A. Delacourte. 1997. Neurofibrillary tangles in Gerstmann-StrausslerScheinker syndrome with the Alai 17-->Val prion gene mutation. J. Neurol. Neurosurg. Psych. 63:240-246.

Zahn, R., A. Liu, T. Luhrs, R. Rick, C. V. Schroetter, F. L. Garcia, M. Billeter, L. Calzolai, G. Wide, and K. Wuthrich. 2000. NMR solution structure of the human prion protein. Proc. Natl. Acad. Sci. U. S. A. 97:145-150.

Zuegg, J., and J. E. Gready. 1999. Molecular dynamics simulations of human prion protein: importance of correct treatment of electrostatic interaction. Biochemistry. 38:13862-13876.

Noriaki Okimoto,* Kazunori Yamanaka,t Atsushi Suenaga,* Masayuki Hata,t and Tyuji Hoshinot

*Advanced Computing Center, Computational Science Division, Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan; tGraduate School of Pharmaceutical Sciences, 1-33 Yayoi-cho, lnage-ku, Chiba University, Chiba 263-8522, Japan; and Computational Research Biology Center, 2-41-6 Ohme, Koutou-ku, Tokyo 135-0064, Japan

Address reprint requests to Noriaki Okimoto, Advanced Computing Center Computational Science Division, Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. Tel.: 81-48. 467-9417; Fax: 81-48-467-4078; E-mail:

(D 2002 by the Biophysical Society 0006-3495/02/0512746/12 $2.00

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