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Review
. 2019 Sep;176(18):3611-3621.
doi: 10.1111/bph.14672. Epub 2019 May 20.

The potential of memory enhancement through modulation of perineuronal nets

James A Duncan  1 , Richard Foster  1   2 , Jessica C F Kwok  3   4
Affiliations
Review

The potential of memory enhancement through modulation of perineuronal nets

James A Duncan et al. Br J Pharmacol. 2019 Sep.

Abstract

With an increasingly aging global population, the incidence of neurological diseases such as dementia is set to increase to unmanageable levels, yet there are currently only symptomatic therapies available for treatment. The mechanisms underlying the development of some forms of dementia, such as Alzheimer's disease (AD), are not yet completely elucidated with several competing hypotheses existing. During the closure of the critical period in the brain, significant compositional changes occur to the neural extracellular matrix (ECM). Specifically, condensed mesh-like structures called perineuronal nets (PNNs) form around subsets of neurons and have a profound effect on axonal growth and limit neuronal plasticity. These PNNs act as a morphological checkpoint and can influence memory and cognition. Manipulating these important ECM structures may provide the key to reactivating plasticity and restoring memory, both of which are severely impaired in AD and other associated neurological diseases. This review explores the current understanding of how PNNs are manipulated and examines potential new methods for PNN modulation. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Composition of the PNNs around the neuron. The HA forms a mesh‐like backbone to which other ECM molecules can bind. HA is attached to the cell surface through HAS as well as other cell surface HA receptors (not shown). The CSPGs ‐ aggrecan, verisican, brevican and neurocan ‐ are all able to attach to chains of HA through link proteins. The CNS‐exclusive tenascin, TN‐R, can conjugate up to three lecticans, enhancing the overall rigidity of the PNNs
Figure 2
Figure 2
(a) The disaccharide repeat of CS. (b) Traditional and systematic nomenclature for various forms of CS present in the ECM
Figure 3
Figure 3
Summary of current methods for modulating PNNs
See this image and copyright information in PMC

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