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Publications

Recent publications in prominent journals including Nature Medicine and Cell highlight the progress being made.

Johns Hopkins's researchers studying LRRK2, a protein whose mutant overactive form can lead to Parkinson's disease. Understanding the mechanism of LRRK2's activity allows researchers to search for drugs to target LRRK2. In the August 22, 2010, issue of Nature Medicine our scientists reported that certain drugs can inhibit LRRK2. A few of inhibitors of LRRK2 provided protection against nerve cell death, a symptom of Parkinson's disease. Two of the drugs, when injected into mice showing Parkinson's disease-like changes in their brain, provided protection against nerve cell death. This makes inhibition of LRRK2 a promising target for human drug development for the treatment of Parkinson's disease. Read about it here:

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease.
Lee BD, Shin JH, VanKampen J, Petrucelli L, West AB, Ko HS, Lee YI, Maguire-Zeiss KA, Bowers WJ, Federoff HJ, Dawson VL, Dawson TM.
Nat Med. 2010 Sep;16(9):998-1000. Epub 2010 Aug 22. PMID:20729864

Other research shows that a drug already used for human cancer treatment could lead to the development of a treatment for Parkinson's disease. In the September 21, 2010 issue of the Proceedings of the National Academy of Sciences (PNAS) our scientists report the findings that a protein called c-Abl disrupts the protein parkin, a protein that protects brain cells from being destroyed. By disrupting parkin function, c-Abl allows for brain cell death that contributes to Parkinson's disease. Commercially available cancer treatment drugs, such as imatinib (Gleevec), already exist that target c-Abl. This means that a brain-permeable c-Abl inhibitor could be a promising treatment for Parkinson's disease. Read about it here:

Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function.
Ko, H.S., Lee, Y., Shin, J.H., Karuppagounder, S.S., Gadad, B.S., Koleske, A.J., Pletnikova, O., Troncoso, J.C., Dawson, V.L., and Dawson, T.M.
Proc. Natl. Acad. Sci. USA 2010 Sep; 21(107):16691'16696

A recent study published March 4, 2011 in Cell identified a key player in brain cell death as a result of parkin inactivation. PARIS, a toxic protein, accumulates when the protective protein parkin is disabled. This leads to brain cell death increasing the progression of Parkinson's disease. This makes PARIS a new target to develop treatment to slow or halt the progression of Parkinson's disease. Read about it here:

PARIS (ZNF746) Repression of PGC-1a Contributes to Neurodegeneration in Parkinson's disease.
Shin et al., Cell (2011), doi:10.1016/j.cell.2011.02.010

These studies, taken together, show the many recent advances made by our Udall Center investigators to understand the mechanisms causing Parkinson's disease and to find treatment targets to slow or halt the disease.

More Publications

Dr Crain's Publications

Co-existence of Parkinson's disease and progressive supranuclear palsy: case report and a review of the literature.
Abhinav K, Marsh L, Crain B, Reich SG, Biglan K.
Neurol Sci. 2011 Feb;32(1):159-63. Epub 2010 Aug 25.

Age, Alzheimer's disease and dementia in the Baltimore Longitudinal Study of Ageing.
Dolan D, Troncoso J, Resnick SM, Crain BJ, Zonderman AB, O'Brien RJ.
Brain. 2010 Aug;133(Pt 8):2225-31. Epub 2010 Jul 20.

Neuropathologic studies of the Baltimore Longitudinal Study of Aging (BLSA).
O'Brien RJ, Resnick SM, Zonderman AB, Ferrucci L, Crain BJ, Pletnikova O, Rudow G, Iacono D, Riudavets MA, Driscoll I, Price DL, Martin LJ, Troncoso JC.
J Alzheimers Dis. 2009;18(3):665-75.

Morphometry of the human substantia nigra in ageing and Parkinson's disease.
Rudow G, O'Brien R, Savonenko AV, Resnick SM, Zonderman AB, Pletnikova O, Marsh L, Dawson TM, Crain BJ, West MJ, Troncoso JC.
Acta Neuropathol. 2008 Apr;115(4):461-70. Epub 2008 Feb 23.

Dr Dawson's publications

PARIS (ZNF746) Repression of PGC-1α Contributes to Neurodegeneration in Parkinson's Disease
Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, Troconso JC, Dawson VL, Dawson TM.
Cell. 2011; 144(5): 689-702.

Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function
Ko HS, Lee Y, Shin JH, Karuppagounder SS, Gadad BS, Koleske AJ, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM.
Proc. Natl. Acad. Sci. U.S.A. 2010; 107(38): 16691-16696.

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease
Lee BD, Shin JH, Vankampen J, Petrucelli L, West AB, Ko HS, Lee YI, Maguire-Zeiss KA, Bowers WJ, Federoff HJ, Dawson VL, Dawson TM.
Nat Medicine. 2010; 16(9): 998-1000.

Genetic animal models of Parkinson's disease
Dawson TM, Ko HS, Dawson VL.
Neuron. 2010; 66(5):646-661.

PINK1 dependent recruitment of Parkin to mitochondria in mitophagy
Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magran' J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S.
Proc. Natl. Acad. Sci. U.S.A. 2009; 107(1): 378-383.

S-nitrosylation of XIAP compromises neuronal survival in Parkinson's disease
Tsang AH, Lee YI, Ko HS, Savitt JM, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM, Chung KK.
Proc. Natl. Acad. Sci. U.S.A. 2009; 106(12): 4900-4905.

CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity
Ko HS, Bailey R, Smith WW, Liu Z, Shin JH, Lee YI, Zhang YJ, Jiang H, Ross CA, Moore DJ, Patterson C, Petrucelli L, Dawson TM, Dawson VL.
Proc. Natl. Acad. Sci. U.S.A. 2009; 106 (8): 2897-2902.

DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase
Andres-Mateos E, Perier C, Zhang L, Blanchard-Fillion B, Greco TM, Thomas B, Ko HS, Sasaki M, Ischiropoulos H, Przedborski S, Dawson TM, Dawson VL.
Proc. Natl. Acad. Sci. U.S.A. 2007; 104(37): 14807-14812.

Ms. Gerstenhaber's publications

Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: A pilot open-label study
Laura Marsh, Kevin Biglan, Melissa Gerstenhaber, James R. Williams.
Movement Disorders 2009; 6 (2): 277'282.

Dr Ko's Publications

CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity.
Ko HS, Bailey R, Smith WW, Liu Z, Shin JH, Lee YI, Zhang YJ, Jiang H, Ross CA, Moore DJ, Patterson C, Petrucelli L, Dawson TM, Dawson VL.
Proc. Natl. Acad. Sci. U.S.A. 2009; 106 (8): 2897-2902.

S-nitrosylation of XIAP compromises neuronal survival in Parkinson's disease.
Tsang AH, Lee YI, Ko HS, Savitt JM, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM,Chung KK.
Proc. Natl. Acad. Sci. U.S.A. 2009; 106(12): 4900-4905.

PINK1 dependent recruitment of Parkin to mitochondria in mitophagy.
Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magran' J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S.
Proc. Natl. Acad. Sci. U.S.A. 2009; 107(1): 378-383.

Genetic animal models of Parkinson's disease.
Dawson TM, Ko HS, Dawson VL.
Neuron. 2010; 66(5):646-661.

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease.
Lee BD, Shin JH, Vankampen J, Petrucelli L, West AB, Ko HS, Lee YI, Maguire-Zeiss KA, Bowers WJ, Federoff HJ, Dawson VL, Dawson TM.
Nat Medicine. 2010; 16(9): 998-1000.

Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function.
Ko HS, Lee Y, Shin JH, Karuppagounder SS, Gadad BS, Koleske AJ, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM.
Proc. Natl. Acad. Sci. U.S.A. 2010; 107(38): 16691-16696.

Repression of PGC-1α Contributes to Neurodegeneration in Parkinson's Disease.
Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, Troconso JC, Dawson VL, Dawson TM.
Cell. 2011; 144(5): 689-702.

Dr Mari's Publications

Scientific and ethical issues related to deep brain stimulation for disorders of mood, behavior, and thought.
Rabins P, Appleby BS, Brandt J, DeLong MR, Dunn LB, Gabri'ls L, Greenberg BD, Haber SN, Holtzheimer PE 3rd, Mari Z, Mayberg HS, McCann E, Mink SP, Rasmussen S, Schlaepfer TE, Vawter DE, Vitek JL, Walkup J, Mathews DJ.
Arch Gen Psychiatry. 2009 Sep;66(9):931-7.

Dr Troncoso's Publications

Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2.
Ramonet D, Daher JP, Lin BM, Stafa K, Kim J, Banerjee R, Westerlund M, Pletnikova O, Glauser L, Yang L, Liu Y, Swing DA, Beal MF, Troncoso JC, McCaffery JM, Jenkins NA, Copeland NG, Galter D, Thomas B, Lee MK, Dawson TM, Dawson VL, Moore DJ.
PLoS One. 2011 Apr 6;6(4):e18568.

Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function.
Ko HS, Lee Y, Shin JH, Karuppagounder SS, Gadad BS, Koleske AJ, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM.
Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16691-6. Epub 2010 Sep 7.

Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse model.
Smith WW, Liu Z, Liang Y, Masuda N, Swing DA, Jenkins NA, Copeland NG, Troncoso JC, Pletnikov M, Dawson TM, Martin LJ, Moran TH, Lee MK, Borchelt DR, Ross CA.
Hum Mol Genet. 2010 Jun 1;19(11):2087-98. Epub 2010 Feb 25.

Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions.
Van Deerlin VM, Sleiman PM, Martinez-Lage M, Chen-Plotkin A, Wang LS, Graff-Radford NR, Dickson DW, Rademakers R, Boeve BF, Grossman M, Arnold SE, Mann DM, Pickering-Brown SM, Seelaar H, Heutink P, van Swieten JC, Murrell JR, Ghetti B, Spina S, Grafman J, Hodges J, Spillantini MG, Gilman S, Lieberman AP, Kaye JA, Woltjer RL, Bigio EH, Mesulam M, Al-Sarraj S, Troakes C, Rosenberg RN, White CL 3rd, Ferrer I, Llad' A, Neumann M, Kretzschmar HA, Hulette CM, Welsh-Bohmer KA, Miller BL, Alzualde A, Lopez de Munain A, McKee AC, Gearing M, Levey AI, Lah JJ, Hardy J, Rohrer JD, Lashley T, Mackenzie IR, Feldman HH, Hamilton RL, Dekosky ST, van der Zee J, Kumar-Singh S, Van Broeckhoven C, Mayeux R, Vonsattel JP, Troncoso JC, Kril JJ, Kwok JB, Halliday GM, Bird TD, Ince PG, Shaw PJ, Cairns NJ, Morris JC, McLean CA, DeCarli C, Ellis WG, Freeman SH, Frosch MP, Growdon JH, Perl DP, Sano M, Bennett DA, Schneider JA, Beach TG, Reiman EM, Woodruff BK, Cummings J, Vinters HV, Miller CA, Chui HC, Alafuzoff I, Hartikainen P, Seilhean D, Galasko D, Masliah E, Cotman CW, Tu''n MT, Mart'nez MC, Munoz DG, Carroll SL, Marson D, Riederer PF, Bogdanovic N, Schellenberg GD, Hakonarson H, Trojanowski JQ, Lee VM.
Nat Genet. 2010 Mar;42(3):234-9. Epub 2010 Feb 14.

Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein.
Lin X, Parisiadou L, Gu XL, Wang L, Shim H, Sun L, Xie C, Long CX, Yang WJ, Ding J, Chen ZZ, Gallant PE, Tao-Cheng JH, Rudow G, Troncoso JC, Liu Z, Li Z, Cai H.
Neuron. 2009 Dec 24;64(6):807-27.

Dr Pletnikova's publications

Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2
Ramonet D, Daher JP, Lin BM, Stafa K, Kim J, Banerjee R, Westerlund M, Pletnikova O, Glauser L, Yang L, Liu Y, Swing DA, Beal MF, Troncoso JC, McCaffery JM, Jenkins NA, Copeland NG, Galter D, Thomas B, Lee MK, Dawson TM, Dawson VL, Moore DJ.
PLoS One. 2011 Apr 6;6(4):e18568.

Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function
Ko HS, Lee Y, Shin JH, Karuppagounder SS, Gadad BS, Koleske AJ, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM.
Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16691-6. Epub 2010 Sep 7.

S-nitrosylation of XIAP compromises neuronal survival in Parkinson's disease
Tsang AH, Lee YI, Ko HS, Savitt JM, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM, Chung KK.
Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4900-5. Epub 2009 Mar 9. Erratum in: Proc Natl Acad Sci U S A. 2009 May 26;106(21):8791.

Morphometry of the human substantia nigra in ageing and Parkinson's disease
Rudow G, O'Brien R, Savonenko AV, Resnick SM, Zonderman AB, Pletnikova O, Marsh L, Dawson TM, Crain BJ, West MJ, Troncoso JC.
Acta Neuropathol. 2008 Apr;115(4):461-70. Epub 2008 Feb 23.

Dr Pontone's publications

Screening for cognitive impairment in Parkinson's disease using the Mattis Dementia Rating Scale
Pontone GM, Palanci J, Williams JR, Bassett SS.
Journal of Neuropsychiatry and Clinical Neurosciences 2011; in Review.

Familial aggregation of panic disturbances in Parkinson's disease
Pontone GM, Palanci J, Bienvenu OJ, Liang KY, Nestadt G, Rabins PV, Williams JR, Marsh L.
Parkinsonism and Related Disorders 2011; in Review.

Anxiety and self-perceived health status in Parkinson's disease
Pontone GM, Williams J, Anderson K, Chase G, Goldstein S, Grill S, Hirsch E, Lehmann S, Little J, Margolis R, Rabins P, Weiss H, Marsh L.
Parkinsonism and Related Disorders 2011; Accepted.

Prevalence of Minor Psychotic Symptoms in a Community-Based Parkinson's Disease Sample
Mack J, Rabins P, Anderson K, Goldstein S, Grill S, Hirsch E, Lehmann S, Little J, Margolis R, Palanci J, Pontone G, Weiss H, Williams J, Marsh L.
American Journal of Geriatric Psychiatry 2010; in Accepted.

Prevalence of anxiety disorders and anxiety subtypes in patients with Parkinson's disease
Pontone GM, Williams J, Anderson K, Chase G, Goldstein S, Grill S, Hirsch E, Lehmann S, Little J, Margolis R, Rabins P, Weiss H, Marsh L.''
Movement Disorders 2009 May 7;24(9):1333-1338.

 
 
 
 
 
 

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