Are paradoxical cell cycle activities in neurons and glia related to the metabolic theory of Alzheimer's disease?
The progression and outcome of neurological diseases are determined by the balance between neurodegeneration, neuroprotection, and neuroregeneration. In this context, astroglial cells are invariably involved in every kind of neuropathology. Mitotically, active glial cells provide metabolic support to active neurons, contribute to coupling between synaptic activity and local blood flow, and thus protect against oxidative stress. Disturbances of the complex neuron-glia interrelation are increasingly recognized as a potentially important pathophysiological mechanism in a wide variety of neurological disorders including those marked by neurodegeneration. Peripheral insulin resistance-mediated increased oxidative stress in glial cells, and consequent DNA damage, induces senescence in glial cells leads to the development of an inflammatory environment. The immune mediators released by senescent (activated) glial cells are considered to be neurotoxic and ultimately increase the oxidant load of neurons. While the neuron is viewed as the prototypical post-mitotic, fully differentiated cell, certain subsets of neurons reactivate cell-cycle activity in response to triggers of neuronal apoptosis, such as genotoxic stress generated by redox changes due to pathological alterations in supporting astroglial cells. Thus, a paradoxical cell cycle block in glial cells coupled with concomitant cell cycle re-entry in neurons (due to pathological alterations created by peripheral insulin resistance-induced neuroendocrine signaling changes) may cause neurodegeneration, such as seen in Alzheimer's disease.
Erol
Adnan
A
Anatolia Hospital, Department of Internal Medicine, Silivri-Istanbul, Turkey. eroladnan@hotmail.com
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D006801:Humans; D009457:Neuroglia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*