SYNAPSE FORMATION, STABILITY and REPAIR

SYNAPSE FORMATION, STABILITY and REPAIR

Searching for molecules with essential functions at synapses

SYNAPSE FORMATION, STABILITY and REPAIR Image 1

We have shown that NMJs degenerate with advancing age, a likely contribute to loss of muscle mass. We have also demonstrated that exercise, caloric restriction, resveratrol and metformin slow and even reverse NMJ aging (Valdez G, PNAS 2010; Stockinger, Journal of Gerontology 2017).

Neuromuscular Junction Repair

A main goal of our lab is to identify the initial cellular and molecular changes that precipitate degeneration of the neuromuscular junction (NMJ). The NMJ is essential for the function and viability of skeletal muscles. Discoveries from our and other labs have shown that deleterious changes at NMJs contribute to loss of muscle mass and degeneration of motor neurons in ALS and during aging. We are thus actively pursuing targetable molecular mechanisms to protect and repair NMJs in ALS and during aging.

Glial Cells in Synapse Regulation

Glial cells play essential roles in the development, stability and repair of synapses. However, the lack of tools to specifically visualize and target glial cells associated with synapses has slowed discovery of molecules they use to promote the development, stability and repair of synapses. We are leveraging markers specific to perisynaptic Schwann cells (PSCs) our lab recently generated to identify mechanisms these cells use to affect NMJs. We are also leveraging these markers to develop culture assays to accelerate the discovery of molecules to treat conditions that affect the NMJ and other synapses, such as ALS and Alzheimer’s Disease. 

SYNAPSE FORMATION, STABILITY and REPAIR Image 2

Perisynaptic Schwann cells (yellow cells), synaptic glia, labeled with two different fluorescence proteins (Castro R, eLife 2020).