Molecular Mechanisms of

Motor Neuron Survival and NMJ Maintenance in ALS

We are looking for enthusiastic and highly motivated graduate students and Post-docs.
  Interested candidates, please send a mail with cv to:
Eran Perlson,
eranpe@tauex.tau.ac.il  

Overview 

Neuron cell death and synapse disruption seen in neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) is a non-cell-autonomous process and involves a multi-system progression.

 

As neurons are highly polarized cells with very long axons, in order to maintain healthy and function properly neurons depend on accurate and efficient long-distance communication mechanisms.​ The long-term goal of the lab is to elucidate the molecular communication mechanisms in the neuron and between the neuron to its environment.  

 

We wish to understand how the long-distance signaling process is regulated and what information is required to maintain healthy nerve cells.​ To achieve this, we are trying to solve questions such as:

Why do alterations in this information lead to neurodegenerative disease? What are the delivery mechanisms for long-distance signaling? How do nerve cells coordinate this information? How does the information know-how get to the right place at the right time and at the right intensity?

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Spinal-cord motoneurons (MN) extend axons over long distances to form neuromuscular junctions (NMJs) with muscle cells. During neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), there is considerable synapse/neuromuscular junction (NMJ) disruption and neuronal cell death. The mechanistic understanding for axons and NMJs maintenance and degeneration is still not fully understood. 

One of the fundamental tasks of a cell, in order to control its fate and function, is to create a dynamic system of spatial specificity and fidelity of signaling pathways that can respond to internal or external changes over space and time. Cell signal must be at the right place and at the right time, alterations in its specific localization may lead to dysfunction and death

Such spatiotemporal regulation of signaling and metabolic activity can be largely achieved by:

1. axonal transport process

2. local protein synthesis mechanisms

To better understand these molecular mechanisms, we built a novel NMJ on a Chip microfluidic platform with motoneuron cell bodies in one compartment and muscle cells in the other, connected via motor axons extending through microgrooves that form functional NMJs. This platform allows precise control, monitoring, and manipulation of subcellular microenvironments, thus opening new possibilities for experimental analyses of long-distance signaling and NMJs biology.

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.

Our current efforts are focused on studying molecular mechanisms of:

  • Local protein synthesis in Axons and NMJs

  • Axonal RNA transport in health and disease

  • Mitochondrial maintenance at the NMJs

  • The role of muscle exosomes in NMJs maintenance

  • Retrograde signaling and motor neuron survival

  • The role of phase separation and condensate in local synthesis at axon/NMJ 

  • Neurotropic spatiotemporal signaling events in health and disease  

Lab Techniques approaches include:  

  • Molecular and cellular neurobiology

  • Microscopy 

  • Microfluidics and lab on a chip 

  • Tg mice models

  • Human iPSC biology 

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