Cell Clocks and Neuronal Networks: Neuron Ticking and Synchronization in Aging and Aging-Related Neurodegenerative Disease
Marta Bonaconsa, Valeria Colavito, Fabien Pifferi, Fabienne Aujard, Esther Schenker, Sophie Dix, Gigliola Grassi-Zucconi, Marina Bentivoglio and Giuseppe Bertini
Affiliation: Department of Neurological and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
Body function rhythmicity has a key function for the regulation of internal timing and adaptation to the environment.
A wealth of recent data has implicated endogenous biological rhythm generation and regulation in susceptibility
to disease, longevity, cognitive performance. Concerning brain diseases, it has been established that many molecular
pathways implicated in neurodegeneration are under circadian regulation. At the molecular level, this regulation relies on
clock genes forming interconnected, self-sustained transcriptional/translational feedback loops. Cells of the master circadian
pacemaker, the hypothalamic suprachiasmatic nucleus, are endowed with this molecular clockwork. Brain cells in
many other regions, including those which play a key role in learning and memory, as well as peripheral cells show a circadian
oscillatory behavior regulated by the same molecular clockwork. We here address the question as to whether intracellular
clockwork signaling and/or the intercellular dialogue between “brain clocks” are disrupted in aging-dependent
neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. The potential implications of clock
genes in cognitive functions in normal conditions, clinical disturbances of circadian rhythms, and especially the sleepwake
cycle, in aging-dependent neurodegenerative diseases and data in animal models are reviewed. The currently limited
knowledge in this field is discussed in the context of the more extensive body of data available on cell clocks and molecular
clockwork during normal aging. Hypotheses on implications of the synchronization between brain oscillators in information
processing in neural networks lay ground for future studies on brain health and disease.
Keywords: Clock genes, sleep, cognitive impairment, Alzheimer’s disease, Parkinson’s disease, circadian rhythms, suprachiasmatic
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