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Program Director, Neurodegenerative Diseases, Center for Health Sciences
Amy Manning-Bog earned her Ph.D. in molecular and cell biology and biochemistry from the University of Missouri, Kansas City. After a post-doctoral fellowship in neuropharmacology at Wayne State University in Detroit, Michigan, and a second fellowship at the Parkinson’s Institute to investigate neurodegenerative mechanisms in Parkinson's disease, she joined Renovis, Inc., a biotechnology company, as a scientist. She investigated novel therapeutic targets for neurodegenerative disorders before returning to the Parkinson’s Institute as assistant professor. Manning-Bog then joined SRI. She has written more than 15 research publications.
Manning-Bog’s research focuses on intersecting mechanisms of degenerative disorders of the central nervous system, including Parkinson’s disease (PD), Alzheimer’s disease (AD), PD-dementia, Gaucher disease, and amyotrophic lateral sclerosis. Certain mutations in the redox-sensitive protein DJ-1 are linked to autosomal recessive forms of parkinsonism; however, DJ-1 modifications are detected in sporadic forms of PD and AD as well as other neurodegenerative diseases presenting with cognitive impairment. Manning-Bog’s group develops new models of DJ-1 deficiency to evaluate whether DJ-1 or its related pathways contribute to the development of mixed tau/alpha-synuclein pathology and related cognitive behavioral deficits.
Another example of a shared mechanism of degeneration is indicated by studies showing increased risk of PD in individuals carrying mutations for Gaucher disease. Manning-Bog’s group also focuses on the relationship between Gaucher disease and PD to determine whether similar mechanisms of toxicity, specifically involving alpha-synuclein-lipid interactions, underlie neuronal damage in both disorders.
Another commonality among risk factors for neurodegenerative diseases is environmental influence, particularly gene-environment interactions. A third arm of Manning-Bog’s research studies involves the impact of environmental modifiers and aging on genetic disposition, including LRRK2-related vulnerability using transgenic models of altered human LRRK2 expression.
Lastly, Manning-Bog’s group evaluates preclinical efficacy and mechanism(s) of action for a variety of putative therapeutic compounds for neurodegenerative disease. Through the study of gene-environment interactions and shared mechanisms of toxicity/pathology comes a better understanding of potential therapeutic targets for debilitating neurodegenerative disorders.
Manning-Bog AB, Schule B, Langston JW (2009) Alpha-synuclein-glucocerebrosidase interactions in pharmacological Gaucher models: a biological link between Gaucher disease and parkinsonism. Neurotoxicology 30:1127-1132.
Manning-Bog AB, Caudle WM, Perez XA, Reaney SH, Paletzki R, Isla MZ, Chou VP, McCormack AL, Miller GW, Langston JW, Gerfen CR, Dimonte DA (2007) Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter. Neurobiol Dis 27:141-150.
Manning-Bog AB, Langston JW (2007) Model fusion, the next phase in developing animal models for Parkinson's disease. Neurotox Res 11:219-240.
Manning-Bog AB, Reaney SH, Chou VP, Johnston LC, McCormack AL, Johnston J, Langston JW, Di Monte DA (2006) Lack of nigrostriatal pathology in a rat model of proteasome inhibition. Ann Neurol 60:256-260.
Li J, Zhu M, Manning-Bog AB, Di Monte DA, Fink AL (2004) Dopamine and L-dopa disaggregate amyloid fibrils: implications for Parkinson's and Alzheimer's disease. Faseb J 18:962-964.
Goers J, Manning-Bog AB, McCormack AL, Millett IS, Doniach S, Di Monte DA, Uversky VN, Fink AL (2003) Nuclear localization of alpha-synuclein and its interaction with histones. Biochemistry 42:8465-8471.
Manning-Bog AB, McCormack AL, Purisai MG, Bolin LM, Di Monte DA (2003) Alpha-synuclein overexpression protects against paraquat-induced neurodegeneration. J Neurosci 23:3095-3099.
Manning-Bog AB, McCormack AL, Li J, Uversky VN, Fink AL, Di Monte DA (2002) The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem 277:1641-1644.
McCormack AL, Thiruchelvam M, Manning-Bog AB, Thiffault C, Langston JW, Cory-Slechta DA, Di Monte DA (2002) Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 10:119-127.
Bannon MJ, Pruetz B, Manning-Bog AB, Whitty CJ, Michelhaugh SK, Sacchetti P, Granneman JG, Mash DC, Schmidt CJ (2002) Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers. Proc Natl Acad Sci U S A 99:6382-6385.