In the spring 2012 I retired from service in clinics, and my role as Neurology Chief. My full focus is on research and fundraising to pursue better treatments, and ultimately, cures for neurodegenerative diseases.
Dr. Young and her late husband (John B. Penney, Jr.) provided the most widely cited model of basal ganglia function (the basal ganglia are the brain regions affected by Huntington's (HD) and Parkinson's (PD) diseases). The model has provided the springboard for testing novel interventions in HD, PD and related disorders.
Dr. Young established the MassGeneral Institute for Neurodegenerative Disease (MIND). MIND brings together scientists at Mass General concentrating on studies of Alzheimer's, PD, HD and amyotrophic lateral sclerosis.Dr. Young spearheaded the comprehensive drug discovery efforts at the MIND and has been successful in identifying drug targets for PD, HD and other neurodegenerative diseases.
Dr. Young received an MD and a PhD in Pharmacology from Johns Hopkins, and then completed residency training in neurology at the University of California, San Francisco. After 13 years on the neurology faculty at the University of Michigan, she was recruited to Mass General as its first female chief at the hospital. Dr. Young holds membership in the Institute of Medicine, the American Academy of Arts and Sciences. She is also the only person (male or female) to have been president of both the international Society for Neuroscience and the American Neurological Association.
My laboratory focuses on studies of basal ganglia disorders, specifically Parkinson's disease and Huntington's diseases. We study each of these diseases independently but also as two of the main diseases affecting the basal ganglia, the part of the brain involved in complex motor movements and behaviors. A major question is: how do the basal ganglia work to affect motor and cognitive behavior in general and then specifically how do areas of the basal ganglia malfunction in the disease process? Understanding these fundamentals will lead us to new therapies in the future.
In Parkinson's disease, we happened on the finding that male and female mRNA and proteins are differentially expressed in the brain and that the disease process affects the sexes differently. Epidemiologically this is also the case. We have found that males and females process alpha-synucelin differently and we hope that by defining the target of these differences, that we well come up with an effective intervention. We are using postmortem human brain tissue, LC-MS and size exclusion chromatography along with immunoprecipitation and Western blotting to understand these gender differences.
We are also looking at the biochemical changes that occur in the brains of parkinsonian animals that have developed levo-dopa-induced dyskinesias. One such protein is TRH which is differentially expressed in the brains of those with dyskinesias.
In Huntington's disease, we have found that the protein, huntingtin, immunoprecipitates with mGluR receptors and homer and we are studying the mechanism and consequences of these interaction.
1. Zucker B, Kama JA, Kuhn A, et al. Decreased Lin7b Expression in Layer 5 Pyramidal Neurons May Contribute to Impaired Corticostriatal Connectivity in Huntington Disease. J Neuropathol Exp Neurol.
2. Orlando LR, Ayala R, Kett LR, et al. Phosphorylation of the homer-binding domain of group I metabotropic glutamate receptors by cyclin-dependent kinase 5. J Neurochem 2009.
3. Young AB. Four decades of neurodegenerative disease research: how far we have come! J Neurosci 2009;29(41):12722-12728.
4. Crittenden JR, Cantuti-Castelvetri I, Saka E, et al. Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy. Proc Natl Acad Sci U S A 2009;106(8):2892-2896.
5. Cha JH, Kosinski CM, Kerner JA, et al. Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci U S A 1998;95(11):6480-6485.
6. Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci 1989;12(10):366-375.
ANNE YOUNG, MD, PHD, chief of Neurology, made history for women in academic medicine by making a $1 million gift to the Department of Neurology through a deferred charitable gift annuity.
MGH Hotline 6.10.11 A world-renowned neurological researcher and clinician who has helped break down barriers for women in her field, Anne B. Young, MD, PhD, chief of the Department of Neurology, has a great deal of wisdom and insight to offer to colleagues.
THE MGH WILL WELCOME new chiefs for the Department of Neurology and the Department of Urology later this spring.