With a major focus on the early pathophysiology of adult-onset diseases such as movement disorders and dementia, his laboratory aims to develop neuroprotective treatments. Our projects include behavioural studies in rodents, electrophysiology and cell biology in acute brain slices, primary neuronal co-cultures and patient stem cell-derived neuron models.
A strong theme has emerged from studying several proteins harbouring mutations听that are autosomal dominantly linked to Parkinson鈥檚 disease, in other words, genes transmitted down the family line that are highly predictive for developing PD. There are several proteins that cause 鈥渇amilial PD,鈥� e.g. LRRK2, VPS35 and synuclein. Milnerwood's laboratory听is听finding that these proteins are involved in the same cellular functions. By learning more about what these proteins are supposed to do and what goes wrong with the mutations present, Milnerwood hopes to work out the common neuronal dysfunction of many forms of parkinsonism and then develop appropriate treatments.
Working out how neuronal function goes awry early in disease states can help听to intervene and possibly to prevent the onset or progression of degenerative processes.听The world鈥檚 population is aging. By 2025, half of the population may be over 60 years old, and up to 2% might have Alzheimer鈥檚 or Parkinson鈥檚 disease. There is a pressing societal and financial need to learn more about, and to better treat, human neurodegenerative disease.
Austen Milnerwood is always looking to recruit talented and enthusiastic individuals at all levels, austen.milnerwood [at] mcgill.ca (please contact) for details regarding current opportunities
Selected publications
Volpicelli-Daley LA, Abdelmotilib H, Liu Z, Stoyka L, Daher JP,听Milnerwood听AJ, Unni VK, Hirst WD, Yue Z, Zhao HT, Fraser K, Kennedy RE, West AB.(2016)听G2019S-LRRK2 Expression Augments 伪-Synuclein Sequestration into Inclusions in Neurons.听J Neurosci.听
Volta M., Cataldi, S., Beccano-Kelly D.A., Munsie L.N., Tatarnikov I., Chou P., Bergeron S., Mitchell E., Lim R., Khinda, J.,听Lloret A., Bennett C.F., Paradiso C., Morari M., Farrer M.J. &听Milnerwood听A.J. (2015)听Chronic and acute LRRK2 silencing has no long-term behavioral effects, whereas wild-type and mutant LRRK2 overexpression induce motor and cognitive deficits and altered regulation of dopamine release.听Parkin. & Rel. dis.听
Volta M,听Milnerwood听AJ, Farrer MJ. (2015)听Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson's disease.听Lancet Neurol.听
Beccano-Kelly D.A., Volta M., Munsie L.N., Paschall S. A., Tatarnikov I., Co K., Chou P., Cao L.P., Bergeron S., Mitchell E., Han H., Melrose H.L., Tapia L., Raymond L.A., Farrer M.J. &听Milnerwood听A.J. (2015)听LRRK2 overexpression alters presynaptic glutamatergic plasticity, striatal dopamine tone, postsynaptic signal transduction, behavioral activity and long-term memory.听Hum Mol Gen.
Munsie L.N.,听Milnerwood听A.J.,听Seibler, P.听Beccano-Kelly D.A.,听Tatarnikov I.T.,听Kindah, J.,听Volta M.,听Kadgien C., Cao L.P., Tapia L. Klein C.听& Farrer M.J. (2015)听Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson鈥檚 Disease VPS35 mutation p.D620N.听Hum Mol Gen.听
Beccano-Kelly D.A., Kuhlmann, N., Tatarnikov I., Volta M., Munsie L.N., Chou P., Cao L.P., Han H., Tapia L.,Farrer M.J. &听Milnerwood听A.J.听(2014)听Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice.听Front. Cell. Neurosci.听
Brigidi G.S., Sun Y.,听Beccano-Kelly D.A., Pitman K., Borgland S.L.,听Milnerwood听A.J.听& Bamji S.X. Delta-catenin Palmitoylation is Essential for Activity-dependent Enhancements of Synapse Structure and Efficacy听(2014).听Nat Neurosci.听
Milnerwood听A. J., Parsons M., Young F., Singaraja, R.,听Volta M.,听Bergeron S., Hayden, M.R. & Raymond, L. A. (2013) Cognitive deficits and severe disruption of synaptic transmission and plasticity in HIP14 palmitoyl transferase knock-out mice.听PNAS听
Milnerwood听A.J., *Kaufman A.M., Sepers M., Gladding C.M., Fan, J., Coquinco, A., Zhang L.Y., Wang L., Qoi J., Lee H., Cynader, M. & Raymond L.A. (2012) Mitigation of augmented extrasynaptic NMDAR signaling and apoptosis in cortico-striatal co-cultures from Huntington鈥檚 disease mice.Neurobiol Dis.听
Kaufman A.M., *Milnerwood听A.J., Sepers M., Coquinco A., She K., Wang L., Lee H., Craig A.M., Cynader M. & Raymond L.A. (2012) Opposing roles of synaptic and extrasynaptic NMDA receptor signaling in striatal and cortical neurons.听J. Neurosci.听
Petkau T., Neal S.J.,听Milnerwood听A. J., Mew A., Hill A.M., Orban P., Gregg J., Lu H., Feldman H.H., Mackenzie I.R.A., Raymond L.A. & Leavitt B.R. (2012). Synaptic dysfunction in progranulin-deficient mice.听Neurobiol.Dis.
Tapia L.,听Milnerwood听A. J., Guo A., Mills F., Yoshida E., Vasuta O.C, Mackenzie I., Raymond, L. A., Cynader M., Jia W., Bamji S.X. (2011).听PGRN Deficiency Decreases Neural Connectivity But Enhances Synaptic Transmission at Individual Synapses.听J. Neurosci.听
Raymond LA, Andr茅 VM, Cepeda C, Gladding CM,听Milnerwood听AJ, Levine MS. (2011)听Pathophysiology of Huntington's disease: time-dependent alterations in synaptic and receptor function.听Neuroscience.听
Milnerwood听A. J.听, Gladding C. M., Pouladi M. A., Kaufman A.M., Hines R. M., Boyd听 J., Ko R.W.Y., Vasuta O. C., Graham R. K., Hayden M. R., Murphy T. H. & Raymond L. A. (2010). Early increase in extrasynaptic NMDA receptor signalling and expression contributes to phenotype onset in Huntington's disease mice.听Neuron
Milnerwood听A. J.听& Raymond L. A. (2010). Early Synaptic Pathophysiology in Neurodegeneration: Insights from Huntington鈥檚 disease.听Trends in Neurosciences听
Milnerwood听A. J.听& Raymond, L. A. (2007). Corticostriatal Synaptic Function in Mouse Models of Huntington's Disease: Early Effects of Huntingtin Repeat Length and Protein Load.听J. Physiol.听
Cummings D. M.,听Milnerwood听A. J., Dall茅rac G.M., Vatsavayai S. C., Hirst M. C. & Murphy, K. P. (2007). Abnormal cortical synaptic plasticity in mice transgenic for human Huntington's disease mutation.听Brain. Res. Bull.
Milnerwood听A. J., Cummings D. M., Dall茅rac G.M., Brown J. Y., Vatsavayai S. C., Hirst M. C., Rezaie P. & Murphy, K. P. (2006). Early development of aberrant synaptic plasticity in a mouse model of Huntington鈥檚 disease.听Hum. Mol. Gen.
