Membrane Organization and Dynamics by Amitabha Chattopadhyay

Author:Amitabha Chattopadhyay
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

9.9 Biomedical Implications

Keeping synaptic strength at an adequate level is a functional requisite of both peripheral and central nervous system synapses, and it is the combination and homeostasis of the +/− mechanisms outlined above that concertedly operate to maintain the functionally adequate density of neurotransmitter receptors. The mechanisms utilized by cells to achieve this equilibrium are complex, and vary between peripheral and CNS. A common feature is the transient immobilization of receptors in nanoscale compartments of the synapse as opposed to extrasynaptic regions, commonly achieved by clustering or by interaction with scaffolding non-receptor proteins and lipid platforms. Our ability to interrogate the dynamics of receptors is currently limited to brief glimpses of the molecules’ entire lifetime, from synthesis to degradation, but nonetheless these snapshots provide useful hints about the organization and the functionally relevant spatiotemporal behavior of these important molecules in the synapse.

Several neurological and neuropsychiatric disorders have been associated with dysfunction of receptors and ion channels at the synapse, whose alterations can be encompassed under the term “synaptopathies”. Diseases like depression, anxiety disorders, various forms of dementia, epilepsy, Parkinson’s disease, autism spectrum disorder, migraine, fragile X syndrome, and schizophrenia are among these disorders, which cover a wide spectrum of pathological synaptic phenotypes, ranging from alterations in the number, size or morphology of dendritic spines, disposition of spines along the dendritic arborizations, etc. The related physiological alterations in these synaptopathies (either hypo- or hyper-function of the synapse) are assumed to depend in turn on the underlying dysfunction of the receptors and channels, the so-called channelopathies [147], which should now be extended to encompass scaffolding and other non-receptor proteins e.g. those misfolded and aggregated at the synapse, like in Alzheimer’s, Huntington’s or Parkinson’s diseases (for recent reviews see e.g. [148, 149]).

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