Massachusetts General Hospital

Research Description

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. We focus on a natural class of compounds known as purines, in particular the role of three purines — adenosine, caffeine and urate — and how targeting them may prevent or slow the brain cell degeneration of Parkinson’s.

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 A_2A 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 dyiskinesia) 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 in order to maximize their impact on the lives of Parkinson’s disease patients.

Principal Investigator

Michael A. Schwarzschild, MD, PhD
Director, Molecular Neurobiology Laboratory
Associate Professor of Neurology,
Harvard Medical School
Associate in Neurology,
Massachusetts General Hospital

Research Scientists

• Chen, Xiqun, Instructor
• Cipriani, Sara, Postdoctoral Fellow
• Kachroo, Anil, Instructor
• Wu, Guanhui, Visiting Scientist

Research Assistants & Technicians

• Desjardins, Cody, Technician
• McClurg, Lauren, Project Manager/Technician
• Xu, Yuehang, Senior Technologist

Lab Group Photos 2011

2010 Molecular Neurobiology Laboratory (MNL) BBQ

Lab Group Photos 2010

2010 Molecular Neurobiology Laboratory (MNL) BBQ

2010 Joint Group Retreat with Ascherio neuroepidemiology group

Updated 9/10/2011

Adenosine/Caffeine Project

Models of Neurodegeneration

Using models of neurodegeneration, this part of the project seeks to understand how adenosine A_2A receptor antagonists, including caffeine, protect neurons in models of Parkinson’s disease.

Proposed mechanism of symptomatic anti-parkinsonian action of adenosine A_2A antagonists

Schwarzschild, Fuxe, Agnati, Chen & Morelli (2006) TRENDS in Neurosciences

Models of Dyskinesia

Using models of dyskinesia this part of the project looks at how adenosine A_2A receptor antagonists may prevent development of dyskinesias.

Taking advantage of the discrete localization of CNS A_2A receptors

Schwarzschild, Fuxe, Agnati, Chen & Morelli (2006) TRENDS in Neurosciences (Adapted)

Urate Project

This project explores how genetic and pharmacological manipulation of the urate pathway may reduce neurodegeneration in models of Parkinson’s disease.

Search for current opportunities on the Mass General careers website at http://www.massgeneral.org/careers/default.aspx or e-mail MGHMIND-jobs.

Gender differences in Parkinson’s disease

Drs. Anne B. Young, Ippolita Cantuti-Castelvetri and Michael Schwarzschild study gender differences in Parkinson’s disease from three different investigative approaches.

E Pluribus Unum for Parkinson Disease - Researchers Draw on Sources to Improve Treatment of PD

What do Gaucher’s disease, gout, and amyloid plaques have in common? For researchers at the MGH, each of them may shed light on the causes and treatment of Parkinson’s disease.

NeuroBlast

NeuroBlast: the newsletter of translational neuroscience and clinical care advances in neurology, neurosurgery, and neuroscience from Massachusetts General Hospital.

Selected Publications

1. 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 A_2A adenosine receptor inactivation in a model of Parkinson's disease. J Neurosci 21:RC143:1-6.
2. 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.
3. Xiao D, Bastia E, Xu YH, Benn CL, Cha JH, Peterson TS, Chen JF & Schwarzschild MA. (2006) Forebrain adenosine A_2A receptors contribute to L-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice. J Neurosci. 26:13548-13555.
4. 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.
5. 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 Neurol 65(6):doi:10.1001/archneur.2008.65.6.nct70003.

NCBI PubMed Publications

Molecular Neurobiology Laboratory: Michael A. Schwarzschild, MD, PhD

Phone: 617-764-9611
Email: michaels@helix.mgh.harvard.edu

Public Transportation Access: no
Disabled Access: yes

Michael A. Schwarzschild, MD, PhD
E-mail: michaels@helix.mgh.harvard.edu

Lab Phone: 617-726-5714