Prof. Eran Perlson

 Department of Physiology and Pharmacology, Sackler Faculty of Medicine , 

Molecular Mechanisms of Neurodegeneration

The lab is a new multi-disciplinary molecular and cellular neurobiology lab. The lab uses state-of-the-art single molecule live imaging techniques on neuronal cultures, as well as biochemistry, cell biology and biophysics approaches on mouse model systems to study the role of axonal transport in neurodegenerative diseases, with an initial focus on ALS.

Neuronal survival and proper function depends on cell-cell communication mediated by ligand-receptor mechanisms. During neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), there is considerable synapse/neuromuscular junction (NMJ) disruption and neuronal cell death. It is non-autonomous processes involve interactions between the neurons to its diverse extracellular microenvironments. The molecular basis for this neuronal dysfunction and death is still poorly understood. One possible reason is alterations in the nature, directed movement and spatial localization of vital extra and intracellular signals.

The long-term research goal of the lab is to understand the vital molecular communications mechanisms between the neurons and its environment. More specifically, we seek to understand the role that retrograde signaling plays in (1) neuronal survival and (2) synapse stability.

We believe that our research will generate novel insights into neurodegenerative mechanisms and ultimately, provide a molecular basis for new drugs as well as delivery methods to treat a range of neurodegenerative diseases.

Gershoni-Emek, N., Mazza A, Gradus T., Sharan R. and Perlson E. (2016) Proteomic analysis of dynein interactors in synaptosomes reveals a role for the RNA-binding protein Staufen1 in Amyotrophic Lateral Sclerosis. Mol Cell Proteomics. 15:506-22.

Ionescu A, Zahavi E, and Perlson E. (2016) A microfluidic system for studying muscle-neuron communication and neuromuscular junction maintenance. Eur J Cell Biol.95:69-88.

Gluska S, Chein M, Rotem N, Ionescu A and Perlson E. (2016) Tracking quantum-dot labeled neurotropic factors transport along primary neuronal axons in compartmental microfluidic chambers. Methods Cell Biol. 2016;131:365-87.

Zahavi E, Ionescu A, Ben-Yaakov K., Gluska S, and Perlson E. (2015) Spatial aspects of GDNF functions revealed in a compartmentalized microfluidic neuromuscular co-culture system. J Cell Sci, 128:1241-52.

Bauer A., Nolden T., Nemitz S., Perlson E. and Finke S. (2015) A dynein light chain 1 binding motif in RABV polymerase L protein plays a role in microtubule reorganization and viral primary transcription. J Virol. 89(18):9591-600.

Bornstein B., Zahavi E., Gelley S., Zoosman M., Yaniv S., Fuchs O., Porat Z., Perlson E. and Schuldiner O. (2015) Developmental axon pruning requires destabilizing of cell adhesion by JNK signaling. Neuron. 88:926-40.

Gluska S, Zahavi E, Chein M, Gradus T, Bauer A, Finke S and Perlson E. (2014). Rabies virus hijacks and accelerates the p75ntr retrograde axonal transport machinery. Plos Pathogen. 10:e1004348.

Bauer A., Nolden T., Römer-Oberdörfer A.,Gluska S., Perlson E. and Finke S (2014). Post-replicative glycoprotein dependent bi-directional rabies virus transport in dorsal root ganglion neurons. J Virol. 15;88.

Dadon- Nachum M, Ben-Yaacov K., Ben- Zur T. Barhum Y., Yaffe D. Perlson E. and Offen D. (2014). Transplanted modified muscle progenitor cells expressing a mixture of neurotrophic factors delay disease onset and enhance survival of ALS model SOD1 mice. J Molec Neurosci. [Epub ahead of print]

Bauer A., Nolden T., Römer-Oberdörfer A., Gluska S.,  Perlson E., and Finke S (2014).  Post-replicative glycoprotein dependent bi-directional rabies virus transport in dorsal root ganglion neurons. J Virol. 15;88.

Gluska S, Zahavi E, Chein M, Gradus T, Bauer A, Finke S and Perlson E. (2014). Rabies virus hijacks and accelerates the p75NTR retrograde axonal transport machinery. PloS Pathogen. 10:e1004348 .

Lilo E, Wald S, Solmesky L, Ben Yaakov K, Gershoni- Emek N, Gotkine M, Karosis D, Bulvik S, Perlson E and Weil M. (2013). Characterization of human sporadic ALS biomarkers in the familial transgenic mSOD1G93A mouse model. Hum Mol Genet. 22:4750-5.

Yashunsky V, Kharilker L, Zahavi E, Mercone S, Golosovskii M, Perlson E, Davidov D, Aroeti B (2013) Real-time sensing of enteropathogenic E. coli-induced effects on epithelial host cell height, cell-substrate interactions, and endocytic processes by infrared surface plasmon spectroscopy. PLoS One. 8:e78431

Perlson E, Hendricks AG, Wilson MH, Lazarus JE, Ben-Yaacov K, Zhang X, Xiang X, Holzbaur EL. (2013). Dynein interacts with NCAM180 to tether and stabilize synaptic microtubules. J Biol Chem. 27;288:27812-24

Castle M, Perlson E, Holzbaur EL, Wolf JH, (2013) Long-distance axonal transport of AAV9 is driven by dynein and kinesin-2 and is trafficked in a highly motile Rab7-positive compartment. Mol Therapy. 22:554-66.

Hendricks AG, Lazarus JE, Perlson E, Gardner MK, Odde DJ, Goldman YE, Holzbaur EL (2012) Dynein tethers and stabilizes dynamic microtubule plus ends. Curr Biol. 22:632-637.

Hendricks, A.*/Perlson, E.*, Ross, J., Schroeder, H., Tokito, M., Holzbaur, E. (2010) Motor coordination via tug-of war mechanism drives bidirectional vesicle transport. Curr Biol. 20: 697-702. *Equally contributing authors

Reviews and Chapters

Guillermo MA., Gershoni-Emek, N., Perlson E and Bronfman FC. (2016). Neurodegeneration and Alzheimer's disease, What can proteomics tell us about the Alzheimer's brain?" Mol Cellular Proteomics. 15:409-25.

Gershoni-Emek, N., Zahavi EE., Gluska S., Slobodskoy Y and Perlson E. (2015) The Molecular Communication Mechanism of Neuron Survival and Synapse Maintenance. (Book chapter, University of Chicago Press), In press.

Gershoni-Emek, N., Chein, M., Gluska, S., Perlson, E. (2015). Amyotrophic Lateral Sclerosis as a Spatiotemporal Mislocalization Disease: Location, Location, Location. In: Jeon, K.W. (Ed.), International Review of Cell and Molecular Biology, pp. 23–71.

Gluska S, Finke S, Perlson, E. (2015) Rabies Express: Receptor-Mediated Increase in Rabies Virus Axonal Transport. Neuronal Regeneration Research. 10:883-4.

Gershoni-Emek, N., Zahavi EE., Gluska S., Slobodskoy Y and Perlson E. (2014) The Molecular Communication Mechanism of Neuron Survival and Synapse Maintenance. In press.