UCLA researchers have developed new major histocompatibility complex class I (MHCI)-based treatments to modulate neuronal outgrowth that may be used to promote neurorepair and inhibit neurodegeneration.
Major histocompatibility complex (MHC) molecules are cell surface molecules that are key players in the immune system and have been mostly studied in the context of immune system cells, or leukocytes. More recently, MHCI has been found to play a critical role in modulating neuronal synaptogenesis and outgrowth.
Researchers at UCLA discovered that recombinant soluble MHCI/peptide proteins acted as “stop signals” for neuronal outgrowth. Conversely, over-expression of MHC heavy chain in neurons promoted neurite outgrowth, suggesting that heavy chain cis interactions with other neuronal molecules can promote neuritogenesis while MHCI/peptide interactions with MHCI receptors can inhibit axon outgrowth. Therefore, blocking MHCI/peptide interactions with their receptors, or enhancing MHCI heavy chain expression, are promising candidates for promoting neurorepair or inhibiting neurodegenerative diseases.
• Enhanced expression of MHCI heavy chain in cultured neurons led to faster neurite outgrowth and more primary neurites.
• Transgenic mice with enhanced MHCI heavy chain expression had significantly better recovery of locomotor abilities after spinal cord injury than wild-type mice.
• Neurons naturally shed soluble MHCI/peptide molecules that inhibit neurite outgrowth, but this could be prevented by addition of anti-MHCI antibodies.
|United States Of America||Issued Patent||7,553,484||06/30/2009||2000-118|
Major histocompatibility complex (MHC), neuro-degenerative, degenerative, neurorepair, brain injury, central nervous system (CNS), synaptogenesis, Alzheimers disease, Parkinsons disease, spinal cord injury, retina, ganglion, perforant path lesion model, lateral geniculate nucleus, neuron, synaptic plasticity, neural activity