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Review
. 2017 Nov 10:11:626.
doi: 10.3389/fnins.2017.00626. eCollection 2017.

Cognitive Decline in Neuronal Aging and Alzheimer's Disease: Role of NMDA Receptors and Associated Proteins

Jesús Avila  1   2 , María Llorens-Martín  1   2 , Noemí Pallas-Bazarra  1   2 , Marta Bolós  1   2 , Juan R Perea  1   2 , Alberto Rodríguez-Matellán  1   2 , Félix Hernández  1   2
Affiliations
Review

Cognitive Decline in Neuronal Aging and Alzheimer's Disease: Role of NMDA Receptors and Associated Proteins

Jesús Avila et al. Front Neurosci. .

Abstract

Molecular changes associated with neuronal aging lead to a decrease in cognitive capacity. Here we discuss these alterations at the level of brain regions, brain cells, and brain membrane and cytoskeletal proteins with an special focus in NMDA molecular changes through aging and its effect in cognitive decline and Alzheimer disease. Here, we propose that some neurodegenerative disorders, like Alzheimer's disease (AD), are characterized by an increase and acceleration of some of these changes.

Keywords: cognition; dendritic spines; neurotransmitter agents; tau proteins; therapies.

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Figures

Figure 1
Figure 1
Partial view of actin cytoskeleton in dendritic spines. Scaffold proteins involved in anchoring of NMDA receptors to actin cytoskeleton. NMDAR, N-methyl-D-aspartate receptor; PSD-95, post-synaptic density protein 95; GKAP, guanylate kinase-associated protein; Shank, SH3 and ankyrin repeat-containing protein; SPAR, spine-associated RapGAP; KALI-7, kalirin-7.
Figure 2
Figure 2
Proposed movement, by lateral diffusion, of NMDA receptors from dendritic spines to extrasynaptic sites. Unbalance between synaptic and extrasynaptic NMDAR may contribute to cognitive decline in neuronal aging and neurodegenerative diseases as Alzheimer disease.
Figure 3
Figure 3
Indirect interaction between Aβ and tau through the NMDA receptor and fyn kinase. Two of the main molecular markers involved in Alzheimer disease, Aβ and tau, may require for their toxic effects of NMDAR-PSD-95 playing a role the kinase Fyn to alter post-synaptic density.
Figure 4
Figure 4
Different levels to study the changes that occur in the brain during aging. An alteration at any of these levels can cause cognitive impairment.
See this image and copyright information in PMC

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