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Ageing, Neuronal Connectivity and Brain Disorders: An Unsolved Ripple Effect

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Abstract

Cognitive decline associated with ageing and age-related disorders emerges as one of the greatest health challenges in the next decades. To date, the molecular mechanisms underlying the onset of neuronal physiological changes in the central nervous system remain unclear. Functional MRI and PET studies have indicated the decline in working memory performance in older adults. Similarly, age-related disorders, such as Alzheimer’s disease, are associated with changes in the prefontral cortex and related neural circuitry, which underlines the decline of integrative function between different brain regions. This is mainly attributed to the loss of synaptic connectivity, which is a feature commonly observed in neurodegenerative disorders. In humans, the morphological and functional changes in neurons, such as reduction of spine numbers and synaptic dysfunction, precede the first signs of cognitive decline and likely contribute to pathology progression. Thus, a new scenario emerges in which apparently unrelated diseases present common features, such as the remodelling of neuronal circuitries promoted by ageing. For many years, ageing was considered a process of slow deterioration triggered by accidental environmental factors. Conversely, it is now evident that ageing is a biological process tightly controlled by evolutionary highly conserved signalling pathways. Importantly, genetic mutations that enhance longevity significantly delay the loss of synaptic connectivity and, therefore, the onset of age-related brain disorders. Accordingly, tweaking ageing might be an attractive approach to prevent cognitive decline caused by age-related synaptic dysfunction.

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Acknowledgement

The authors want to thank Prof. di Monte, Dr. Troulinaki and Miss Belau for their precious comments.

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Authors and Affiliations

  1. Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ludwig-Erhard-Allee 2, 53175, Bonn, Germany

    Daniele Bano & Pierluigi Nicotera

  2. MRC Toxicology Unit, University of Leicester, Leicester, UK

    Massimiliano Agostini & Gerry Melino

  3. Biochemistry Laboratory, IDI-IRCCS, University of Rome Tor Vergata, Rome, Italy

    Gerry Melino

  4. European Brain Research Institute, Rome, Italy

    Gerry Melino

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  1. Daniele Bano
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  2. Massimiliano Agostini
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  4. Pierluigi Nicotera
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Corresponding authors

Correspondence to Daniele Bano or Pierluigi Nicotera.

Additional information

We would like to dedicate this review to Prof Rita Levi-Montalcini in recognition of her fundamental contribution to science.

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Bano, D., Agostini, M., Melino, G. et al. Ageing, Neuronal Connectivity and Brain Disorders: An Unsolved Ripple Effect. Mol Neurobiol 43, 124–130 (2011). https://doi.org/10.1007/s12035-011-8164-6

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  • DOI: https://doi.org/10.1007/s12035-011-8164-6

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