Enhancing synaptogenesis in diseases characterized by deficiencies in brain synapses
Name
Wurtman-2010-Enhancing synaptogen.pdf
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187.1 KB
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Author(s)
Wurtman, Richard Jay
Date Issued
November 2010
Journal
Frontiers in Psychiatry
Publisher
Frontiers Research Foundation
Citation
Wurtman, Richard J. “Enhancing Synaptogenesis in Diseases Characterized by Deficiencies in Brain Synapses.” Frontiers in Psychiatry 1 (2010).
Version
Final published version
Abstract
The loss of hippocampal and cortical synapses, resulting from impaired synaptogenesis, accelerated synaptic degeneration, or both, is one of the earliest neuropathologic findings in Alzheimer’s Disease and is the finding that best correlates with cognitive symptoms (DeKosky and Scheff, 1990; Terry et al., 1991; Selkoe, 2002). A similar decrease in brain synapses is an early finding in an animal model of AD which overproduces A-beta peptides (Jacobsen et al., 2006), and aggregates of such peptides, applied locally to the brain, can also damage synapses, distort neurites, and decrease the numbers of the dendritic spines which are essential precursors for glutamatergic synapses (Jacobsen et al., 2006; Spires-Jones et al., 2007; Knobloch and Mansuy, 2008). These observations have supported the widely-held view that a treatment that would block the synthesis of A-beta or remove it from the circulation, might – by depleting its levels in brain – slow the loss of synapses in AD and thereby sustain cognitive functions in patients. A generation of creative and diligent researchers has provided us with abundant information about A-beta’s synthesis, fates, and toxic effects, and this information has been used to generate rationally-designed drug candidates for treating the disease. However to date none of these candidates – even ones shown to reduce brain levels of A-beta oligomers and senile plaques – has been successful in sustaining cognition.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.3389/fpsyt.2010.00147
