Mechanism of Synaptic Dysfunction and How This Disruption in IGF-1 homeostasis Leads to Neurodegenerative Diseases: A Theory

Background: The diverse stimuli which ultimately trigger synaptic degeneration, may do so through a single, critical step or related pathways. The identification of such a step could possibly result in a significant breakthrough in our understanding of why synapses are particularly vulnerable. This could assist in the development of clinical strategies that protect synaptic function, possibly providing answers for a broad spectrum of disorders. Methods: We propose that the methodology behind the mystery of synaptic disintegration is found in the 4- dimensional aberrant neurological function. In the CNS this presents as delirium, in the PNS fragility (acquired hospital weakness). Results: Clinically, we observe that the loss of synaptic function may occur faster than the recovery of the neurological circuit, causing a sort of accelerated aging. Further experiments will be required to gain important insight into the molecular mechanism of insulin-like growth factor 1 (IGF-1), its action on presynaptic and postsynaptic neurotransmitter release, and therapeutic ways to mediate this IGF-1 correlated age-associated decline. Further approaches to both observe and possibly correct these synaptic mechanisms include using ultrasound technology, electric stimulation of synaptic circuitry, radio wave, light stimulation, magnetic fields, virtual reality, and other physical methods that can interfere with the human’s internal electrical system, stimulating systems at risk that have lost their synaptic pathways and resetting or preserving homeostatic clinical mechanisms and outcomes. Conclusion: While there are a variety of clinically encountered conditions, such as sedatives, steroids, and immobility, that accelerate the synaptic dysfunction, we hypothesize the main critical pathway is that of Hebbian spike-timing-dependent plasticity (STDP), combining both the temporal element of neural circuitry and the dysregulation of the homeostatic functions that modulate synaptogenesis. The proposed 4D function of the nervous system relies on both timing and usage.