Anna Janas

All Publications

• A Stem Cell Model of the Motor Circuit Uncouples Motor Neuron Death from Hyperexcitability Induced by SMN Deficiency CELL REPORTS Simon, C. M., Janas, A. M., Lotti, F., Tapia, J. C., Pellizzoni, L., Mentis, G. Z. 2016; 16 (5): 1416-1430

  Abstract

  In spinal muscular atrophy, a neurodegenerative disease caused by ubiquitous deficiency in the survival motor neuron (SMN) protein, sensory-motor synaptic dysfunction and increased excitability precede motor neuron (MN) loss. Whether central synaptic dysfunction and MN hyperexcitability are cell-autonomous events or they contribute to MN death is unknown. We addressed these issues using a stem-cell-based model of the motor circuit consisting of MNs and both excitatory and inhibitory interneurons (INs) in which SMN protein levels are selectively depleted. We show that SMN deficiency induces selective MN death through cell-autonomous mechanisms, while hyperexcitability is a non-cell-autonomous response of MNs to defects in pre-motor INs, leading to loss of glutamatergic synapses and reduced excitation. Findings from our in vitro model suggest that dysfunction and loss of MNs result from differential effects of SMN deficiency in distinct neurons of the motor circuit and that hyperexcitability does not trigger MN death.

  View details for DOI 10.1016/j.celrep.2016.06.087

  View details for Web of Science ID 000380749200021

  View details for PubMedID 27452470

  View details for PubMedCentralID PMC4972669

• Exosomes and other extracellular vesicles in neural cells and neurodegenerative diseases BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES Janas, A. M., Sapon, K., Janas, T., Stowell, M. H., Janas, T. 2016; 1858 (6): 1139-1151

  Abstract

  The function of human nervous system is critically dependent on proper interneuronal communication. Exosomes and other extracellular vesicles are emerging as a novel form of information exchange within the nervous system. Intraluminal vesicles within multivesicular bodies (MVBs) can be transported in neural cells anterogradely or retrogradely in order to be released into the extracellular space as exosomes. RNA loading into exosomes can be either via an interaction between RNA and the raft-like region of the MVB limiting membrane, or via an interaction between an RNA-binding protein-RNA complex with this raft-like region. Outflow of exosomes from neural cells and inflow of exosomes into neural cells presumably take place on a continuous basis. Exosomes can play both neuro-protective and neuro-toxic roles. In this review, we characterize the role of exosomes and microvesicles in normal nervous system function, and summarize evidence for defective signaling of these vesicles in disease pathogenesis of some neurodegenerative diseases.

  View details for DOI 10.1016/j.bbamem.2016.02.011

  View details for Web of Science ID 000375356900008

  View details for PubMedID 26874206