Molecular Neurobiology Lab: Michael Schwarzchild, MD, PhD
Molecular Neurobiology Laboratory: Michael A. Schwarzschild, MD, PhD
MassGeneral Institute for Neurodegenerative Disease
Building 114, Charlestown Navy Yard
114 16th Street, Room 3002
Charlestown, MA 02129
Alternate Lab Phone: 617-726-5714
Explore This Lab
The Molecular Neurobiology Laboratory at the MassGeneral Institute for Neurodegenerative Disease, under the direction of Michael Schwarzschild, MD, PhD, investigates molecular mechanisms in mouse models of Parkinson’s disease in an effort to develop improved therapies for Parkinson’s and related neurodegenerative diseases.
The lab is pursuing major epidemiological and clinical clues to the disease through fruitful inter-disciplinary collaborations with the research group of Professor Alberto Ascherio at the Harvard School of Public Health and with the Parkinson Study Group of North America. Caffeine and urate are linked to a lower risk of Parkinson’s and/or to a slower rate of disease progression in humans.
The lab explores how caffeine (and other blockers of the adenosine A2A receptor) and urate may be protecting brain cells in Parkinson’s. We employ complementary pharmacological and genetic (e.g., gene knockout) tools to dissect the role of adenosine and urate pathways in the brains of parkinsonian mice. We are also studying the role of adenosine receptors in the disabling motor complications (abnormal involuntary movements known as dyskinesia) that are sometimes triggered by standard anti-parkinsonian therapy.
Through our well-established translational research network and track record, we expedite transfer of our molecular insights from the laboratory back to the clinic to maximize their impact on the lives of Parkinson’s disease patients.
Models of Neurodegeneration
Using models of neurodegeneration, this part of the project seeks to understand how adenosine A2A receptor antagonists, including caffeine, protect neurons in models of Parkinson’s disease.
Models of Dyskinesia
Using models of dyskinesia this part of the project looks at how adenosine A2A receptor antagonists may prevent development of dyskinesias.
This project explores how genetic and pharmacological manipulation of the urate pathway may reduce neurodegeneration in models of Parkinson’s disease.
Chen JF, Xu K, Petzer JP, Staal R, Xu YH, Beilstein M, Sonsalla PK, Castagnoli K, Castagnoli N Jr, & Schwarzschild MA (2001) Neuroprotection by caffeine and A2A adenosine receptor inactivation in a model of Parkinson's disease.J Neurosci21:RC143:1-6.
Kachroo A, Orlando LR, Grandy DK, Chen JF, Young AB, & Schwarzschild MA. (2005) Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice.J Neurosci. 25:10414-10409.
Xiao D, Bastia E, Xu YH, Benn CL, Cha JH, Peterson TS, Chen JF & Schwarzschild MA. (2006) Forebrain adenosine A2A receptors contribute to L-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice.J Neurosci. 26:13548-13555.
Xu K, Xu Y, Brown-Jermyn D, Chen JF, Ascherio A, Dluzen DE, & Schwarzschild MA. (2006) Estrogen prevents neuroprotection by caffeine in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.J Neurosci. 26:535-41.
Schwarzschild MA, Schwid SR, Marek K, Watts A, Lang AE, Oakes D, Shoulson I, & Ascherio A, and the Parkinson Study Group PRECEPT Investigators. (2008) Serum urate as a predictor of clinical and radiographic progression in Parkinson’s disease.Arch Neurol65(6):doi:10.1001/archneur.2008.65.6.nct70003.
Full NCBI PubMed publications list.
Our Research Team
- Department of Neurology