Neurodegeneration and Protein Misfolding
In most neurodegenerative disorders, disease is caused by a single protein misfolding into a beta-sheet rich conformation that is capable of self-templating and spreading throughout the brain. This mechanism was first described in 1982 by Dr. Stanley Prusiner for the prion protein (PrP). In prion diseases, such as scrapie, chronic wasting disease, or Creutzfeldt-Jakob disease, cellular PrP (PrPC) misfolds into the scrapie conformation (PrPSc) to cause progressive degeneration. More recently, this phenomenon has been seen with a handful of additional proteins, including alpha-synuclein, beta-amyloid, SOD-1, tau, and TDP-43. Research in the Woerman Lab is focused on investigating the formation of alpha-synuclein prions in multiple system atrophy and Parkinson’s disease, as well as tau prion formation in Alzheimer’s disease, chronic traumatic encephalopathy, progressive supranuclear palsy, and other frontotemporal dementias.
Woerman AL, Oehler A, Kazmi SA, Lee J, Halliday GM, Middleton LT, Gentleman SM, Mordes DA, Grinberg LT, Olson SH, and Prusiner SB. Multiple system atrophy prions retain strain specificity after serial propagation in two different Tg(SNCA*A53T) mouse lines. Acta Neuropathol. 2019, 137(3):437- 454.
Woerman AL, Kazmi SA, Patel S, Aoyagi A, Oehler A, Widjaja K, Mordes DA, Olson SH, and Prusiner SB. Familial Parkinson’s point mutation abolishes multiple system atrophy prion replication.Proc Natl Acad Sci USA. 2018, 115(2):409-414.
Woerman AL, Kazmi SA, Patel S, Freyman Y, Oehler A, Aoyagi A, Mordes DA, Halliday GM, Middleton LT, Gentleman SM, Olson SH, and Prusiner SB. MSA prions exhibit remarkable stability and resistance to inactivation.Acta Neuropathol. 2018, 135(1):49-63.
Woerman AL,Patel S, Kazmi SA, Oehler A, Freyman Y, Espiritu L, Cotter R, Castaneda JA, Olson SH, and Prusiner SB. Kinetics of human mutant tau prion formation in the brains of 2 transgenic mouse lines. JAMA Neurol.2017, 74(12):1464-1472.
Woerman AL & Aoyagi A, Patel S, Kazmi SA, Lobach I, Grinberg LT, McKee AC, Seeley WW, Olson SH, and Prusiner SB. Tau prions from Alzheimer’s disease and chronic traumatic encephalopathy patients propagate in cultured cells. Proc Natl Acad Sci USA. 2016, 113(50):E8187-E8196.
Prusiner SB, Woerman AL, Mordes DA, Watts JC, Rampersaud R, Berry DB, Patel S, Oehler A, Lowe JK, Kravitz SN, Geschwind DH, Glidden DV, Halliday G, Middleton LT, Gentleman SM, Grinberg LT, and Giles K. Evidence for a-Synuclein Prions Causing Multiple System Atrophy in Humans with Parkinsonism. Proc Natl Acad Sci USA. 2015, 112(38):E5308-E5317. *Manuscript awarded the Cozzarelli Prize by the National Academy of Sciences (USA).
Woerman AL, Stöhr J, Aoyagi A, Rampersaud R, Krejciova Z, Watts JC, Ohyama T, Patel S, Widjaja K, Oehler A, Sanders DW, Diamond MI, Seeley WW, Middleton L, Gentleman SM, Mordes DA, Südhof TC, Giles K, and Prusiner SB. Propagation of prions causing synucleinopathies in cultured cells. Proc Natl Acad Sci USA. 2015, 112(35):E4949-E4958.
Woerman AL and Mendelowitz D. Postnatal Sulfur Dioxide Exposure Reversibly Alters Parasympathetic Regulation of Heart Rate. Hypertension. 2013, 62(2):274-280.
Gorini CG, Jameson H, Woerman AL, Perry DC, Mendelowitz D. Prenatal Nicotine Exposure Enhances Trigeminocardiac Reflex and Brainstem Pathways via Serotonin Receptor Facilitation. Journal of Applied Physiology. 2013, 115(4):415-421.
Woerman ALand Mendelowitz D. Perinatal Sulfur Dioxide Exposure Alters Brainstem Parasympathetic Control of Heart Rate. Cardiovascular Research. 2013, 99(1):16-23.
Boychuk CR, Woerman AL, and Mendelowitz D. Modulation of bulbospinal rostral ventral lateral medulla neurons by hypoxia/hypercapnia but not medullary respiratory activity. Hypertension. 2012, 6(60):1491-1497.
Giles K,Woerman AL, Prusiner SB. Prions and TSEs. Disinfection, Sterilization, and Preservation, 6th Edition. Editor: Seymour S. Block. In press.
Woerman AL. The importance of developing strain-specific models of neurodegenerative disease. Acta Neuropathol. 2017, 134(5):809-812.
Giles K, Woerman AL, Berry DB, and Prusiner SB. Bioassays and Inactivation of Prions. Cold Spring Harb Perspect Biol. Editor: Stanley B. Prusiner. 2017 Feb 28.
Woerman AL, Watts JC, Aoyagi A, Giles K, Middleton LT, and Prusiner SB. a-Synuclein: Multiple System Atrophy Prions. Cold Spring Harb Perspect Med. Editor: Stanley B. Prusiner. 2017 Feb 17.